Tachykinin Receptor Agonist

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Giovanna Improta - One of the best experts on this subject based on the ideXlab platform.

  • Stimulatory effect of PG-KII, an NK3 Tachykinin Receptor Agonist, on isolated pancreatic acini: species-related differences.
    Peptides, 2004
    Co-Authors: G. Linari, Giovanna Improta, Simona Agostini, A. Andreassi, Maria Broccardo
    Abstract:

    Abstract More information is needed on the physiological role of the Tachykinins (TKs), especially neurokinin 3 -Receptor (NK 3 ) Agonists, in the pancreas. In this paper we investigated and compared the effect of PG-KII (10 −9 to 10 −6  M), a natural NK 3 -Receptor Agonist, with that of the known secretagogues substance P (10 −9 to 10 −6  M), caerulein (10 −11 to 10 −8  M) and carbachol (10 −8 to 10 −5  M), on amylase secretion from dispersed pancreatic acini of the guinea pig and rat. PG-KII (10 −7  M) significantly increased basal amylase release from guinea pig pancreatic acini (from 5.4±0.9% to 11.3±0.5%, P 3 -Receptor antAgonist, SR 142801 (5×10 −7  M), and left unchanged by the NK 1 -Receptor antAgonist, SR 140333 (5×10 −7  M). Conversely, substance P (10 −7  M) significantly stimulated amylase secretion from rat and guinea pig acini (12.6±0.6% and 12.1±0.7%, P 1 -Receptor antAgonist (5×10 −7  M), but not by the NK 3 -Receptor antAgonist (5×10 −7  M). The PG-KII- and substance P-evoked maximal responses were lower than those evoked by caerulein (10 −9  M) (guinea pig, 19.1±1.3%; rat, 18.2±0.9%, P −5  M) (guinea pig, 23.3±1.2%; rat, 24.0±1.1%, P −5  M), phospholipase A 2 quinacrine (10 −5  M), and protein tyrosine kinase genistein (10 −4  M), partly but significantly inhibited PG-KII, as well as carbachol-stimulated amylase release. Coincubation of PG-KII 10 −7  M with submaximal doses of caerulein (10 −11 to 10 −10  M) and carbachol (10 −7 to 10 −6  M) had an additive effect on amylase release. Pre-incubation with PG-KII (10 −7  M) for 30 min significantly reduced the subsequent amylase response to PG-KII, whereas pre-incubation with caerulein 10 −10  M or carbachol 10 −6  M did not. These findings suggest that PG-KII directly contributes to pancreatic exocrine secretion by interacting with acinar NK 3 Receptors of the guinea pig but not of the rat. PG-KII signal transduction involves the intracellular phospholipase C, phospholipase A 2 and protein tyrosine kinase pathways. The NK 3 Receptor system cooperates with the other known secretagogues in regulating guinea pig exocrine pancreatic secretion and undergoes rapid homologous desensitization.

  • Selective Tachykinin NK3-Receptor Agonists stimulate in vitro exocrine pancreatic secretion in the guinea pig
    'Elsevier BV', 2002
    Co-Authors: G. Linari, Maria Broccardo, V Nucerito, Giovanna Improta
    Abstract:

    The Tachykinins, including substance P, neurokinin A and neurokinin B, are a mammalian peptide family that have documented motor, sensory and circulatory neurotransmitter functions in the gut. Little is known about their action on the exocrine pancreas. In this study we investigated the effects of PG-KII, a natural NK3-Tachykinin Receptor Agonist, and senktide, a synthetic NK3-Tachykinin Receptor Agonist, on amylase release from isolated pancreatic lobules of the guinea pig in comparison with the secretagogues carbachol, caerulein and substance P and the depolarizing agent KCl. When added to incubation flasks at various concentrations (from 10(-10) to 10(-6) M), PG-KII and senkfide both caused a dose-dependent increase in amylase release from pancreatic lobules. PG-KII and senktide elicited a lower maximal response (7.5 +/- 0.8 and 8.1 +/- 0.6% of the total lobular amylase content) than carbachol (34.4 +/- 3.9%), caerulein (26.5 +/- 2.8%) and KCl (22.5 +/- 3.8%). Whereas atropine left PG-KII and senktide-stimulated secretion unaffected, the non peptide NK3 Receptor antAgonist SR 142801 significantly reduced the stimulant effect of PG-KII and senktide. PG-KII (10(-7) M) also slightly though significantly increased the response to lower concentrations of caerulein (10(-11) and 10(-10) M) and carbachol (10(-7) and 10(-6) M). These findings show that PG-KII and senkfide are weak stimulants of exocrine pancreatic secretion that act directly on the acinar cells through NK3 Receptors, without cholinergic involvement. We suggest also that the Tachykininergic NK3 Receptor system cooperates with the other known secretagogues in the control of pancreatic exocrine secretion. (C) 2002 Elsevier Science Inc. All rights reserved

  • Selective Tachykinin NK3-Receptor Agonists stimulate in vitro exocrine pancreatic secretion in the guinea pig.
    Peptides, 2002
    Co-Authors: G. Linari, Maria Broccardo, V Nucerito, Giovanna Improta
    Abstract:

    Abstract The Tachykinins, including substance P, neurokinin A and neurokinin B, are a mammalian peptide family that have documented motor, sensory and circulatory neurotransmitter functions in the gut. Little is known about their action on the exocrine pancreas. In this study we investigated the effects of PG-KII, a natural NK 3 -Tachykinin Receptor Agonist, and senktide, a synthetic NK 3 -Tachykinin Receptor Agonist, on amylase release from isolated pancreatic lobules of the guinea pig in comparison with the secretagogues carbachol, caerulein and substance P and the depolarizing agent KCl. When added to incubation flasks at various concentrations (from 10 −10 to 10 −6  M), PG-KII and senktide both caused a dose-dependent increase in amylase release from pancreatic lobules. PG-KII and senktide elicited a lower maximal response (7.5±0.8 and 8.1±0.6% of the total lobular amylase content) than carbachol (34.4±3.9%), caerulein (26.5±2.8%) and KCl (22.5±3.8%). Whereas atropine left PG-KII and senktide-stimulated secretion unaffected, the non peptide NK 3 Receptor antAgonist SR 142801 significantly reduced the stimulant effect of PG-KII and senktide. PG-KII (10 −7  M) also slightly though significantly increased the response to lower concentrations of caerulein (10 −11 and 10 −10  M) and carbachol (10 −7 and 10 −6  M). These findings show that PG-KII and senktide are weak stimulants of exocrine pancreatic secretion that act directly on the acinar cells through NK 3 Receptors, without cholinergic involvement. We suggest also that the Tachykininergic NK 3 Receptor system cooperates with the other known secretagogues in the control of pancreatic exocrine secretion.

  • Inhibitory role on gastric secretion of a central NK-3 Tachykinin Receptor Agonist, senktide.
    Peptides, 1991
    Co-Authors: Giovanna Improta, Maria Broccardo
    Abstract:

    When administered intracerebroventricularly, the highly selective NK-3 Tachykinin Receptor Agonist senktide possesses a potent and dose-related inhibitory effect on gastric acid secretion. The central mechanism governing the antisecretory effect of senktide was examined in perfused-stomach rats by studying its influence on gastric acid secretion elicited by the secretagogues histamine, pentagastrin and bethanechol. Given intracerebroventricularly, senktide reduced the acid response to histamine, but not that to pentagastrin or bethanechol. Stimulation of NK-3 Receptors in rat brain thus appears to inhibit gastric acid secretion through histaminergic pathways.

Maria Broccardo - One of the best experts on this subject based on the ideXlab platform.

  • Stimulatory effect of PG-KII, an NK3 Tachykinin Receptor Agonist, on isolated pancreatic acini: species-related differences.
    Peptides, 2004
    Co-Authors: G. Linari, Giovanna Improta, Simona Agostini, A. Andreassi, Maria Broccardo
    Abstract:

    Abstract More information is needed on the physiological role of the Tachykinins (TKs), especially neurokinin 3 -Receptor (NK 3 ) Agonists, in the pancreas. In this paper we investigated and compared the effect of PG-KII (10 −9 to 10 −6  M), a natural NK 3 -Receptor Agonist, with that of the known secretagogues substance P (10 −9 to 10 −6  M), caerulein (10 −11 to 10 −8  M) and carbachol (10 −8 to 10 −5  M), on amylase secretion from dispersed pancreatic acini of the guinea pig and rat. PG-KII (10 −7  M) significantly increased basal amylase release from guinea pig pancreatic acini (from 5.4±0.9% to 11.3±0.5%, P 3 -Receptor antAgonist, SR 142801 (5×10 −7  M), and left unchanged by the NK 1 -Receptor antAgonist, SR 140333 (5×10 −7  M). Conversely, substance P (10 −7  M) significantly stimulated amylase secretion from rat and guinea pig acini (12.6±0.6% and 12.1±0.7%, P 1 -Receptor antAgonist (5×10 −7  M), but not by the NK 3 -Receptor antAgonist (5×10 −7  M). The PG-KII- and substance P-evoked maximal responses were lower than those evoked by caerulein (10 −9  M) (guinea pig, 19.1±1.3%; rat, 18.2±0.9%, P −5  M) (guinea pig, 23.3±1.2%; rat, 24.0±1.1%, P −5  M), phospholipase A 2 quinacrine (10 −5  M), and protein tyrosine kinase genistein (10 −4  M), partly but significantly inhibited PG-KII, as well as carbachol-stimulated amylase release. Coincubation of PG-KII 10 −7  M with submaximal doses of caerulein (10 −11 to 10 −10  M) and carbachol (10 −7 to 10 −6  M) had an additive effect on amylase release. Pre-incubation with PG-KII (10 −7  M) for 30 min significantly reduced the subsequent amylase response to PG-KII, whereas pre-incubation with caerulein 10 −10  M or carbachol 10 −6  M did not. These findings suggest that PG-KII directly contributes to pancreatic exocrine secretion by interacting with acinar NK 3 Receptors of the guinea pig but not of the rat. PG-KII signal transduction involves the intracellular phospholipase C, phospholipase A 2 and protein tyrosine kinase pathways. The NK 3 Receptor system cooperates with the other known secretagogues in regulating guinea pig exocrine pancreatic secretion and undergoes rapid homologous desensitization.

  • Selective Tachykinin NK3-Receptor Agonists stimulate in vitro exocrine pancreatic secretion in the guinea pig
    'Elsevier BV', 2002
    Co-Authors: G. Linari, Maria Broccardo, V Nucerito, Giovanna Improta
    Abstract:

    The Tachykinins, including substance P, neurokinin A and neurokinin B, are a mammalian peptide family that have documented motor, sensory and circulatory neurotransmitter functions in the gut. Little is known about their action on the exocrine pancreas. In this study we investigated the effects of PG-KII, a natural NK3-Tachykinin Receptor Agonist, and senktide, a synthetic NK3-Tachykinin Receptor Agonist, on amylase release from isolated pancreatic lobules of the guinea pig in comparison with the secretagogues carbachol, caerulein and substance P and the depolarizing agent KCl. When added to incubation flasks at various concentrations (from 10(-10) to 10(-6) M), PG-KII and senkfide both caused a dose-dependent increase in amylase release from pancreatic lobules. PG-KII and senktide elicited a lower maximal response (7.5 +/- 0.8 and 8.1 +/- 0.6% of the total lobular amylase content) than carbachol (34.4 +/- 3.9%), caerulein (26.5 +/- 2.8%) and KCl (22.5 +/- 3.8%). Whereas atropine left PG-KII and senktide-stimulated secretion unaffected, the non peptide NK3 Receptor antAgonist SR 142801 significantly reduced the stimulant effect of PG-KII and senktide. PG-KII (10(-7) M) also slightly though significantly increased the response to lower concentrations of caerulein (10(-11) and 10(-10) M) and carbachol (10(-7) and 10(-6) M). These findings show that PG-KII and senkfide are weak stimulants of exocrine pancreatic secretion that act directly on the acinar cells through NK3 Receptors, without cholinergic involvement. We suggest also that the Tachykininergic NK3 Receptor system cooperates with the other known secretagogues in the control of pancreatic exocrine secretion. (C) 2002 Elsevier Science Inc. All rights reserved

  • Selective Tachykinin NK3-Receptor Agonists stimulate in vitro exocrine pancreatic secretion in the guinea pig.
    Peptides, 2002
    Co-Authors: G. Linari, Maria Broccardo, V Nucerito, Giovanna Improta
    Abstract:

    Abstract The Tachykinins, including substance P, neurokinin A and neurokinin B, are a mammalian peptide family that have documented motor, sensory and circulatory neurotransmitter functions in the gut. Little is known about their action on the exocrine pancreas. In this study we investigated the effects of PG-KII, a natural NK 3 -Tachykinin Receptor Agonist, and senktide, a synthetic NK 3 -Tachykinin Receptor Agonist, on amylase release from isolated pancreatic lobules of the guinea pig in comparison with the secretagogues carbachol, caerulein and substance P and the depolarizing agent KCl. When added to incubation flasks at various concentrations (from 10 −10 to 10 −6  M), PG-KII and senktide both caused a dose-dependent increase in amylase release from pancreatic lobules. PG-KII and senktide elicited a lower maximal response (7.5±0.8 and 8.1±0.6% of the total lobular amylase content) than carbachol (34.4±3.9%), caerulein (26.5±2.8%) and KCl (22.5±3.8%). Whereas atropine left PG-KII and senktide-stimulated secretion unaffected, the non peptide NK 3 Receptor antAgonist SR 142801 significantly reduced the stimulant effect of PG-KII and senktide. PG-KII (10 −7  M) also slightly though significantly increased the response to lower concentrations of caerulein (10 −11 and 10 −10  M) and carbachol (10 −7 and 10 −6  M). These findings show that PG-KII and senktide are weak stimulants of exocrine pancreatic secretion that act directly on the acinar cells through NK 3 Receptors, without cholinergic involvement. We suggest also that the Tachykininergic NK 3 Receptor system cooperates with the other known secretagogues in the control of pancreatic exocrine secretion.

  • Inhibitory role on gastric secretion of a central NK-3 Tachykinin Receptor Agonist, senktide.
    Peptides, 1991
    Co-Authors: Giovanna Improta, Maria Broccardo
    Abstract:

    When administered intracerebroventricularly, the highly selective NK-3 Tachykinin Receptor Agonist senktide possesses a potent and dose-related inhibitory effect on gastric acid secretion. The central mechanism governing the antisecretory effect of senktide was examined in perfused-stomach rats by studying its influence on gastric acid secretion elicited by the secretagogues histamine, pentagastrin and bethanechol. Given intracerebroventricularly, senktide reduced the acid response to histamine, but not that to pentagastrin or bethanechol. Stimulation of NK-3 Receptors in rat brain thus appears to inhibit gastric acid secretion through histaminergic pathways.

Michel R Corboz - One of the best experts on this subject based on the ideXlab platform.

  • Tachykinin nk3 and nk1 Receptor activation elicits secretion from porcine airway submucosal glands
    British Journal of Pharmacology, 2003
    Co-Authors: Jonathan E Phillips, Michel R Corboz
    Abstract:

    We presently characterized the Tachykinin Receptor subtypes, using Tachykinin Receptor Agonists and selective antAgonists, that induce submucosal gland fluid flux (JG) from porcine tracheal explants with the hillocks technique. We also investigated the effects of the Tachykinin Receptor Agonists on the electrophysiologic parameters of the tracheal epithelium in Ussing chambers. The NK1 Tachykinin Receptor Agonist substance P (SP, 1 μM) and the NK3 Tachykinin Receptor Agonist [MePhe7]neurokinin B ([MePhe7]NKB, 1 μM) induced gland fluid fluxes of 0.29±0.03 μl min−1 cm−2 (n=26) and 0.36±0.05 μl min−1 cm−2 (n=24), respectively; while the NK2 Tachykinin Receptor Agonist [βAla8]neurokinin A (4-10) ([βAla8]NKA (4-10), 1 μM) had no effect on JG (n=10). The NK1 Receptor antAgonist CP99994 (1 μM, n=9) blocked 93% of the SP-induced JG, whereas the NK3 Receptor antAgonist SB223412 (1 μM, n=12) had no effect on the SP-induced JG. However, SB223412 (1 μM, n=9) blocked 89% of the [MePhe7]NKB-induced JG while CP99994 (1 μM, n=10) did not affect the [MePhe7]NKB-induced JG. The NK2 Receptor antAgonist SR48968 (1 μM) did not block the JG induced by either the NK1 (n=4) or NK3 (n=13) Receptor Agonists. The nicotinic ganglionic acetylcholine Receptor antAgonist hexamethonium (1 μM) and the muscarinic acetylcholine Receptor antAgonist atropine (1 μM) also decreased the NK3 Receptor Agonist-induced JG by 67% (n=10) and 71% (n=12), respectively. The potential difference (PD), short-circuit current (ISC), and membrane resistance (RM) of the porcine tracheal epithelial membranes were not significantly affected by any of the neurokinin Agonists or antAgonists (1 μM, basolateral) used in this study, although SP and [βAla8]NKA (4-10) induced a slight transient epithelial hyperpolarization. These data suggest that NK1 and NK3 Receptors induce porcine airway gland secretion by different mechanisms and that the NK3 Receptor Agonists induced secretion is likely due to activation of prejunctional NK3 Receptors on parasympathetic nerves, resulting in acetylcholine-release. We conclude that Tachykinin Receptor antAgonists may have therapeutic potential in diseases with pathophysiological mucus hypersecretion such as asthma and chronic bronchitis. Keywords: Mucus, hillock, trachea, Tachykinin Agonists and antAgonists, submucosal gland secretion, porcine airways Introduction The Tachykinin peptides substance P (SP), neurokinin A (NKA), and neurokinin B (NKB) display preferential affinity for the Tachykinin NK1, NK2 and NK3 Receptors, respectively (Maggi, 1995). However, each Tachykinin peptide can act as a full Agonist on all three Receptors, if present at sufficiently high concentrations (Regoli et al., 1994). Activation of airway C-fibre afferent nerves leads to a local release of Tachykinins that elicit many biological effects, including submucosal gland secretion (Joos et al., 2001). These Tachykinins may, therefore, play a role in diseases with characteristic pathophysiological mucus hypersecretion (Rogers, 2002) such as asthma (Joos et al., 2000; Spina & Page, 1996; Spina et al., 1998) whereas chronic bronchitis (Barnes, 2001). In human airways, it is generally agreed that mucus secretion, microvascular leakage, and increased blood flow are mediated by the NK1 Receptors (Piedimonte, 1995) whereas the NK2 Receptors directly mediate bronchoconstriction (Advenier et al., 1992a; Rizzo et al., 1999) and potentiate cholinergic bronchomotor tone (Hey et al., 1996). Tachykinin NK3 Receptors have yet to be identified in the human airways by immunohistochemical techniques (Bai et al., 1995; Baluk et al., 1996), although there is evidence that functional NK3 Receptors are localized on guinea-pig airway parasympathetic ganglion neurons (Myers & Undem, 1993). The literature also suggests that airway peripheral NK3 Receptors modulate airway hyperresponsiveness (Daoui et al., 2000) and cough (Daoui et al., 1998) in guinea-pigs, and inflammatory cell recruitment in mice (Nenan et al., 2001). Previous studies in mucus secretion with selective Tachykinin Receptor antAgonists on ferret (Geppetti et al., 1993; Meini et al., 1993), rat (Wagner et al., 1999), and human (Rogers et al., 1989) tissues showed that the Tachykinin-induced mucus secretory response is mostly mediated via Tachykinin NK1 Receptors. In these studies, the secretagogue effects elicited by activation of NK2 and NK3 Receptors were not significant. However, Nagaki et al. (1994) have shown that activation of NK2 Receptors can induce secretion from isolated cat airway glands, but not from tracheal explants. The submucosal glands present in the proximal airways of large animal species play a critical role in the airway defense mechanisms (Donaldson et al., 2002). In the present study, we determined the Tachykinin Receptor subtypes mediating submucosal gland secretion from pig tracheal epithelium using Tachykinin Agonists and selective antAgonists. Furthermore, the effects of acetylcholine Receptor antAgonists on Tachykinin-induced gland secretion and the effects of Tachykinin Receptor Agonists on transepithelial ion transport were examined. The tissues used in this study were from pigs, large mammals with a dense network of upper airway submucosal glands (Goco et al., 1963; Jones et al., 1975) similar to what is observed in humans (Jeffery, 1983; Choi et al., 2000) but absent in many smaller animal species (Choi et al., 2000). Pig and human airway submucosal glands are also similar with respect to morphology (Goco et al., 1963), density (Phipps, 1981; Phillips et al., 2002a), and the distribution of the different types of mucin (acidic and neutral glycoprotein) they contain (Jones et al., 1975).

Antonio Giachetti - One of the best experts on this subject based on the ideXlab platform.

  • facilitation of reflex micturition by intravesical administration of βala8 neurokinin a 4 10 a selective nk 2 Tachykinin Receptor Agonist
    The Journal of Urology, 1991
    Co-Authors: Carlo Alberto Maggi, Sandro Giuliani, Luigi Abelli, Paolo Santicioli, Antonio Giachetti
    Abstract:

    Abstract We have determined the ability of [βAla 8 ]-NKA(4-l0), a selective Agonist for NK-2 Tachykinin Receptors to stimulate micturition in anesthetized rats and guinea-pigs. In both species, the intravesical instillation of the peptide at μM concentrations reduced bladder capacity and residual volume, indicating a facilitatory effect on reflex micturition. At these concentrations, no plasma extravasation was produced as determined by the Evans blue content of the organ. In experiments on the isolated rat or guinea-pig bladder strips, the NK-2 Receptor Agonist induced powerful contractions. In a in vitro model of the guinea-pig whole bladder the intravesical instillation of the NK-2 Agonist facilitated the occurrence of rhythmic contractile activity. It is concluded from these studies that intravenous administration of [/3Ala 8 ]-NKA(4-10) exerts a facilitatory effect on the micturition reflex, presumably involving the ability of the NK-2 Receptor Agonist to cross the urothelium and stimulate smooth muscle contraction.

  • Facilitation of Reflex Micturition By Intravesical Administration of [βAla8]-Neurokinin A (4–10), A Selective NK-2 Tachykinin Receptor Agonist
    The Journal of urology, 1991
    Co-Authors: Carlo Alberto Maggi, Sandro Giuliani, Luigi Abelli, Paolo Santicioli, Antonio Giachetti
    Abstract:

    Abstract We have determined the ability of [βAla 8 ]-NKA(4-l0), a selective Agonist for NK-2 Tachykinin Receptors to stimulate micturition in anesthetized rats and guinea-pigs. In both species, the intravesical instillation of the peptide at μM concentrations reduced bladder capacity and residual volume, indicating a facilitatory effect on reflex micturition. At these concentrations, no plasma extravasation was produced as determined by the Evans blue content of the organ. In experiments on the isolated rat or guinea-pig bladder strips, the NK-2 Receptor Agonist induced powerful contractions. In a in vitro model of the guinea-pig whole bladder the intravesical instillation of the NK-2 Agonist facilitated the occurrence of rhythmic contractile activity. It is concluded from these studies that intravenous administration of [/3Ala 8 ]-NKA(4-10) exerts a facilitatory effect on the micturition reflex, presumably involving the ability of the NK-2 Receptor Agonist to cross the urothelium and stimulate smooth muscle contraction.

G. Linari - One of the best experts on this subject based on the ideXlab platform.

  • Stimulatory effect of PG-KII, an NK3 Tachykinin Receptor Agonist, on isolated pancreatic acini: species-related differences.
    Peptides, 2004
    Co-Authors: G. Linari, Giovanna Improta, Simona Agostini, A. Andreassi, Maria Broccardo
    Abstract:

    Abstract More information is needed on the physiological role of the Tachykinins (TKs), especially neurokinin 3 -Receptor (NK 3 ) Agonists, in the pancreas. In this paper we investigated and compared the effect of PG-KII (10 −9 to 10 −6  M), a natural NK 3 -Receptor Agonist, with that of the known secretagogues substance P (10 −9 to 10 −6  M), caerulein (10 −11 to 10 −8  M) and carbachol (10 −8 to 10 −5  M), on amylase secretion from dispersed pancreatic acini of the guinea pig and rat. PG-KII (10 −7  M) significantly increased basal amylase release from guinea pig pancreatic acini (from 5.4±0.9% to 11.3±0.5%, P 3 -Receptor antAgonist, SR 142801 (5×10 −7  M), and left unchanged by the NK 1 -Receptor antAgonist, SR 140333 (5×10 −7  M). Conversely, substance P (10 −7  M) significantly stimulated amylase secretion from rat and guinea pig acini (12.6±0.6% and 12.1±0.7%, P 1 -Receptor antAgonist (5×10 −7  M), but not by the NK 3 -Receptor antAgonist (5×10 −7  M). The PG-KII- and substance P-evoked maximal responses were lower than those evoked by caerulein (10 −9  M) (guinea pig, 19.1±1.3%; rat, 18.2±0.9%, P −5  M) (guinea pig, 23.3±1.2%; rat, 24.0±1.1%, P −5  M), phospholipase A 2 quinacrine (10 −5  M), and protein tyrosine kinase genistein (10 −4  M), partly but significantly inhibited PG-KII, as well as carbachol-stimulated amylase release. Coincubation of PG-KII 10 −7  M with submaximal doses of caerulein (10 −11 to 10 −10  M) and carbachol (10 −7 to 10 −6  M) had an additive effect on amylase release. Pre-incubation with PG-KII (10 −7  M) for 30 min significantly reduced the subsequent amylase response to PG-KII, whereas pre-incubation with caerulein 10 −10  M or carbachol 10 −6  M did not. These findings suggest that PG-KII directly contributes to pancreatic exocrine secretion by interacting with acinar NK 3 Receptors of the guinea pig but not of the rat. PG-KII signal transduction involves the intracellular phospholipase C, phospholipase A 2 and protein tyrosine kinase pathways. The NK 3 Receptor system cooperates with the other known secretagogues in regulating guinea pig exocrine pancreatic secretion and undergoes rapid homologous desensitization.

  • Selective Tachykinin NK3-Receptor Agonists stimulate in vitro exocrine pancreatic secretion in the guinea pig.
    Peptides, 2002
    Co-Authors: G. Linari, Maria Broccardo, V Nucerito, Giovanna Improta
    Abstract:

    Abstract The Tachykinins, including substance P, neurokinin A and neurokinin B, are a mammalian peptide family that have documented motor, sensory and circulatory neurotransmitter functions in the gut. Little is known about their action on the exocrine pancreas. In this study we investigated the effects of PG-KII, a natural NK 3 -Tachykinin Receptor Agonist, and senktide, a synthetic NK 3 -Tachykinin Receptor Agonist, on amylase release from isolated pancreatic lobules of the guinea pig in comparison with the secretagogues carbachol, caerulein and substance P and the depolarizing agent KCl. When added to incubation flasks at various concentrations (from 10 −10 to 10 −6  M), PG-KII and senktide both caused a dose-dependent increase in amylase release from pancreatic lobules. PG-KII and senktide elicited a lower maximal response (7.5±0.8 and 8.1±0.6% of the total lobular amylase content) than carbachol (34.4±3.9%), caerulein (26.5±2.8%) and KCl (22.5±3.8%). Whereas atropine left PG-KII and senktide-stimulated secretion unaffected, the non peptide NK 3 Receptor antAgonist SR 142801 significantly reduced the stimulant effect of PG-KII and senktide. PG-KII (10 −7  M) also slightly though significantly increased the response to lower concentrations of caerulein (10 −11 and 10 −10  M) and carbachol (10 −7 and 10 −6  M). These findings show that PG-KII and senktide are weak stimulants of exocrine pancreatic secretion that act directly on the acinar cells through NK 3 Receptors, without cholinergic involvement. We suggest also that the Tachykininergic NK 3 Receptor system cooperates with the other known secretagogues in the control of pancreatic exocrine secretion.

  • Selective Tachykinin NK3-Receptor Agonists stimulate in vitro exocrine pancreatic secretion in the guinea pig
    'Elsevier BV', 2002
    Co-Authors: G. Linari, Maria Broccardo, V Nucerito, Giovanna Improta
    Abstract:

    The Tachykinins, including substance P, neurokinin A and neurokinin B, are a mammalian peptide family that have documented motor, sensory and circulatory neurotransmitter functions in the gut. Little is known about their action on the exocrine pancreas. In this study we investigated the effects of PG-KII, a natural NK3-Tachykinin Receptor Agonist, and senktide, a synthetic NK3-Tachykinin Receptor Agonist, on amylase release from isolated pancreatic lobules of the guinea pig in comparison with the secretagogues carbachol, caerulein and substance P and the depolarizing agent KCl. When added to incubation flasks at various concentrations (from 10(-10) to 10(-6) M), PG-KII and senkfide both caused a dose-dependent increase in amylase release from pancreatic lobules. PG-KII and senktide elicited a lower maximal response (7.5 +/- 0.8 and 8.1 +/- 0.6% of the total lobular amylase content) than carbachol (34.4 +/- 3.9%), caerulein (26.5 +/- 2.8%) and KCl (22.5 +/- 3.8%). Whereas atropine left PG-KII and senktide-stimulated secretion unaffected, the non peptide NK3 Receptor antAgonist SR 142801 significantly reduced the stimulant effect of PG-KII and senktide. PG-KII (10(-7) M) also slightly though significantly increased the response to lower concentrations of caerulein (10(-11) and 10(-10) M) and carbachol (10(-7) and 10(-6) M). These findings show that PG-KII and senkfide are weak stimulants of exocrine pancreatic secretion that act directly on the acinar cells through NK3 Receptors, without cholinergic involvement. We suggest also that the Tachykininergic NK3 Receptor system cooperates with the other known secretagogues in the control of pancreatic exocrine secretion. (C) 2002 Elsevier Science Inc. All rights reserved