The Experts below are selected from a list of 585 Experts worldwide ranked by ideXlab platform
Nigel L. Barnett - One of the best experts on this subject based on the ideXlab platform.
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Endothelin Receptors in the Cornea, Iris and Ciliary Processes. Evidence from Binding, Secondary Messenger and PCR Studies
Experimental Eye Research, 1993Co-Authors: Neville N. Osborne, Nigel L. Barnett, W. LuttmannAbstract:Endothelin (ET)-1 (10 nanoM) is about six times more effective than ET-3 in contracting the isolated Iris Sphincter Muscle; the ET-1-induced contraction is insensitive to indomethacin treatment. The effect of ET-2 is intermediatory between ET-1 and ET-3 in contracting the Muscle. The relative potency of the ETs to stimulate inositol phosphates (InsPs) in the Iris-ciliary processes is ET-1 > ET-2 > ET-3, with ET-1 about six times more potent then ET-3; these effects are also insensitive to indomethacin. Studies utilizing the polymerase chain reaction (PCR) show that ETB receptors are present. Although no evidence could be found for the occurrence of ETA receptors, their presence cannot be excluded. These results suggest that the stimulation of InsPs and contraction of the Iris Sphincter Muscle by ET is mediated by ETB receptors and that products generated via activation of phospholipase A2 are not directly involved in the observed responses. However, another type of ET receptor is indicated by the finding that ET-1 reduced the forskolin-elevated cAMP levels in the Iris-ciliary epithelium. Autoradiographic results show that specific [125I]ET-1 binding sites are associated with the Iris, ciliary processes and the corneal endothelium. As in the Iris-ciliary process tissues, ET-1 is the most effective of the three ETs stimulating InsPs in the cornea, although statistically the differences were insignificant. Moreover, ET-1 was found to have not effect on the forskolin-elevated cAMP levels in the cornea. Whether these results reflect true differences between the ET receptors in the Iris-ciliary processes and corneal endothelium remains to be established.
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endothelin i stimulates phosphatidylinositol hydrolysis in the Iris ciliary complex and is a potent constrictor of the Sphincter Muscle
Experimental Eye Research, 1992Co-Authors: Neville N. Osborne, Nigel L. BarnettAbstract:Endothelin-1 (0.5-10 nM) produced a concentration-related contraction of the isolated Iris Sphincter Muscle. The contraction rate of the Muscle was slower for endothelin than carbachol, but endothelin was also more potent than carbachol, although the maximum contraction size was greater for carbachol. The endothelin response was unaffected by atropine whereas the carbachol effect was abolished. Endothelin-1 and carbachol stimulate the accumulation of inositol phosphates in a concentrationrelated way. The endothelin response was unaffected by atropine, prazosin or ketanserin, but the carbachol effect was specifically-antagonized by atropine. It is suggested that activation of endothelin-1 receptors to stimulate phosphatidylinositol hydrolysis may be the initial phase in the contraction response of the Iris Sphincter Muscle.
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Endothelin-I Stimulates Phosphatidylinositol Hydrolysis in the Iris/Ciliary Complex and is a Potent Constrictor of the Sphincter Muscle
Experimental eye research, 1992Co-Authors: Neville N. Osborne, Nigel L. BarnettAbstract:Endothelin-1 (0.5-10 nM) produced a concentration-related contraction of the isolated Iris Sphincter Muscle. The contraction rate of the Muscle was slower for endothelin than carbachol, but endothelin was also more potent than carbachol, although the maximum contraction size was greater for carbachol. The endothelin response was unaffected by atropine whereas the carbachol effect was abolished. Endothelin-1 and carbachol stimulate the accumulation of inositol phosphates in a concentrationrelated way. The endothelin response was unaffected by atropine, prazosin or ketanserin, but the carbachol effect was specifically-antagonized by atropine. It is suggested that activation of endothelin-1 receptors to stimulate phosphatidylinositol hydrolysis may be the initial phase in the contraction response of the Iris Sphincter Muscle.
Neville N. Osborne - One of the best experts on this subject based on the ideXlab platform.
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Endothelin Receptors in the Cornea, Iris and Ciliary Processes. Evidence from Binding, Secondary Messenger and PCR Studies
Experimental Eye Research, 1993Co-Authors: Neville N. Osborne, Nigel L. Barnett, W. LuttmannAbstract:Endothelin (ET)-1 (10 nanoM) is about six times more effective than ET-3 in contracting the isolated Iris Sphincter Muscle; the ET-1-induced contraction is insensitive to indomethacin treatment. The effect of ET-2 is intermediatory between ET-1 and ET-3 in contracting the Muscle. The relative potency of the ETs to stimulate inositol phosphates (InsPs) in the Iris-ciliary processes is ET-1 > ET-2 > ET-3, with ET-1 about six times more potent then ET-3; these effects are also insensitive to indomethacin. Studies utilizing the polymerase chain reaction (PCR) show that ETB receptors are present. Although no evidence could be found for the occurrence of ETA receptors, their presence cannot be excluded. These results suggest that the stimulation of InsPs and contraction of the Iris Sphincter Muscle by ET is mediated by ETB receptors and that products generated via activation of phospholipase A2 are not directly involved in the observed responses. However, another type of ET receptor is indicated by the finding that ET-1 reduced the forskolin-elevated cAMP levels in the Iris-ciliary epithelium. Autoradiographic results show that specific [125I]ET-1 binding sites are associated with the Iris, ciliary processes and the corneal endothelium. As in the Iris-ciliary process tissues, ET-1 is the most effective of the three ETs stimulating InsPs in the cornea, although statistically the differences were insignificant. Moreover, ET-1 was found to have not effect on the forskolin-elevated cAMP levels in the cornea. Whether these results reflect true differences between the ET receptors in the Iris-ciliary processes and corneal endothelium remains to be established.
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endothelin i stimulates phosphatidylinositol hydrolysis in the Iris ciliary complex and is a potent constrictor of the Sphincter Muscle
Experimental Eye Research, 1992Co-Authors: Neville N. Osborne, Nigel L. BarnettAbstract:Endothelin-1 (0.5-10 nM) produced a concentration-related contraction of the isolated Iris Sphincter Muscle. The contraction rate of the Muscle was slower for endothelin than carbachol, but endothelin was also more potent than carbachol, although the maximum contraction size was greater for carbachol. The endothelin response was unaffected by atropine whereas the carbachol effect was abolished. Endothelin-1 and carbachol stimulate the accumulation of inositol phosphates in a concentrationrelated way. The endothelin response was unaffected by atropine, prazosin or ketanserin, but the carbachol effect was specifically-antagonized by atropine. It is suggested that activation of endothelin-1 receptors to stimulate phosphatidylinositol hydrolysis may be the initial phase in the contraction response of the Iris Sphincter Muscle.
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Endothelin-I Stimulates Phosphatidylinositol Hydrolysis in the Iris/Ciliary Complex and is a Potent Constrictor of the Sphincter Muscle
Experimental eye research, 1992Co-Authors: Neville N. Osborne, Nigel L. BarnettAbstract:Endothelin-1 (0.5-10 nM) produced a concentration-related contraction of the isolated Iris Sphincter Muscle. The contraction rate of the Muscle was slower for endothelin than carbachol, but endothelin was also more potent than carbachol, although the maximum contraction size was greater for carbachol. The endothelin response was unaffected by atropine whereas the carbachol effect was abolished. Endothelin-1 and carbachol stimulate the accumulation of inositol phosphates in a concentrationrelated way. The endothelin response was unaffected by atropine, prazosin or ketanserin, but the carbachol effect was specifically-antagonized by atropine. It is suggested that activation of endothelin-1 receptors to stimulate phosphatidylinositol hydrolysis may be the initial phase in the contraction response of the Iris Sphincter Muscle.
Ryuichi Yamamoto - One of the best experts on this subject based on the ideXlab platform.
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Rho-kinase, but not protein kinase C, is involved in generation of the spontaneous tone in the resting phase of the isolated pig Iris Sphincter Muscle.
Current eye research, 2009Co-Authors: Mayumi Okano, Masamichi Ohkura, Naoko Tanaka, Yoshikazu Uchikawa, Junpei Mutoh, Hiroaki Hisa, Ryuichi YamamotoAbstract:Purpose: The purpose of the present study was to clarify the role of Rho-kinase and/or protein kinase C in the resting tension of the isolated pig Iris Sphincter Muscle. Materials and Methods: The motor activity of the isolated pig Iris Sphincter Muscle was measured isometrically. Results: EGTA, a chelator of extracellular Ca2+, significantly reduced the resting tension. Y27632, a Rho-kinase inhibitor, significantly reduced the resting tension in a concentration-dependent manner. The resting tension diminished by Y27632 was significantly recovered by the addition of calyculin A, a myosin light chain phosphatase (MLCP) inhibitor, in a concentration-dependent manner. GF109203X, a protein kinase C inhibitor, had no effect on the resting tension. Conclusion: These results suggest that, in the isolated pig Iris Sphincter Muscle, Rho-kinase plays an important role in the generation of spontaneous tone in the resting phase via the inhibition of MLCP activity.
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Relaxant effect of adrenomedullin on bovine isolated Iris Sphincter Muscle under resting conditions.
Clinical and experimental pharmacology & physiology, 2005Co-Authors: Y Uchikawa, Hideyuki Kobayashi, Akihiko Wada, M Okano, A Sawada, Y Asada, Nobuhisa Nao-i, Masamichi Ohkura, Naoko Tanaka, Ryuichi YamamotoAbstract:1. The mechanisms involved in the fine adjustment of Iris Sphincter Muscle tone are largely unknown. The aim of the present study was to clarify the effects of adrenomedullin on the resting tension of the bovine isolated Iris Sphincter Muscle. 2. The motor activity of the bovine isolated Iris Sphincter Muscle was measured isometrically. The effects of adrenomedullin on resting tension were analysed in the presence of indomethacin. The presence of adrenomedullin mRNA in the preparation was determined by reverse transcription-polymerase chain reaction. Immunolabelling for adrenomedullin was also performed. 3. Adrenomedullin significantly decreased the resting tension of the Muscle. The relaxant effect of adrenomedullin was significantly inhibited by adrenomedullin (22-52), a putative antagonist for the adrenomedullin receptor, or calcitonin gene-related peptide (CGRP) (8-37), a putative antagonist for the CGRP1 receptor. The relaxant effect was almost completely blocked by a combination of adrenomedullin (22-52) and CGRP (8-37). 4. The relaxant effect of adrenomedullin was also significantly diminished by 2',5'-dideoxyadenosine, an inhibitor of adenylate cyclase, N(G)-nitro-L-arginine, an inhibitor of nitric oxide synthesis, or 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, an inhibitor of soluble guanylate cyclase. 5. Reverse transcription-polymerase chain reaction analysis showed that adrenomedullin mRNA was expressed in the Muscle strip. Immunopositive staining for adrenomedullin was detected in blood vessel cells and in the Iris Sphincter Muscle cells. 6. These results suggest that adrenomedullin may be an autocrine and paracrine regulator of the resting tension of the Iris Sphincter Muscle. Its biological effects may be due to the direct involvement of adrenomedullin receptors and also to the stimulation of CGRP1 receptors. The stimulation of these receptors by the peptide leads to the activation of adenylate cyclase and soluble guanylate cyclase and subsequent relaxation of the Muscle strip.
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Different responsiveness to nitric oxide-cyclic guanosine monophosphate pathway in cholinergic and tachykinergic contractions of the rabbit Iris Sphincter Muscle.
Investigative ophthalmology & visual science, 1997Co-Authors: Hideki Chuman, Hideyuki Kobayashi, A Sawada, Nobuhisa Nao-i, Ryuichi Yamamoto, Chuman T, Akihiko WadaAbstract:Purpose. In the rabbit Iris Sphincter Muscle, sodium nitroprusside (SNP), a nitric oxide (NO) donor, inhibits cholinergic contraction but does not affect tachykinergic contraction in vitro. The objectives of the current study were to clarify the mechanism for the different responsiveness to NO in cholinergic and tachykinergic muscular contractions, and to examine whether the mechanism for NO-induced inhibition of cholinergic muscular contraction is operative in vivo. Methods. Iris Sphincter Muscle was dissected from the rabbit eye pretreated with or without endotoxin (lipopolysaccharide, LPS) in vivo. Cyclic guanosine monophosphate (cGMP) content in the Iris Sphincter Muscle was determined by radioimmunoassay. The motor activity of the ringshaped Iris Sphincter Muscle was measured isometrically. Sodium nitroprusside, carboxy-2-phenyl-4,4,5,5,-tetramethyl-imidazoline-1-oxyl-3-oxide (C-PTIO, a scavenger of NO radicals), and 8-bromo cGMP (a permeable cGMP analogue) were administered between the first and second administrations of carbachol and neurokinin A, both of which had caused sustained contraction in the Iris Sphincter Muscle. Results. Sodium nitroprusside inhibited the contraction of the Iris Sphincter Muscle caused by carbachol but had no effect on the contraction caused by neurokinin A Application of C-PTIO significantly reduced SNP-induced cGMP accumulation in the Muscle, as well as the SNP-induced inhibition of muscular contraction caused by carbachol. Neither carbachol nor neurokinin A influenced SNP-induced cGMP accumulation in the Muscle. Induction of 8-bromo-cGMP significantly diminished the muscular contraction caused by carbachol but not that caused by neurokinin A. In vivo pretreatment of the eye with LPS increased, in a time-dependent manner, the cGMP accumulation in the Iris Sphincter Muscle, which was significantly inhibited by pretreatment of N G -nitro-L-arginine methyl ester (an inhibitor of NO synthesis) in vivo. Conclusions. These results demonstrate that in rabbits the increase in cGMP accumulation induced by NO in the Iris Sphincter Muscle is involved in the cholinergic contraction but not in the tachykinergic contraction, suggesting that different sensitivities to cGMP are essential for the different responsiveness to NO. Furthermore, the results of this study showed that the NO-cGMP pathway is operative in vivo and regulates Iris Sphincter Muscle tone, at least when the eyes are infected with bacteria.
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Nitric oxide-sensitive and -insensitive contractions of the isolated rabbit Iris Sphincter Muscle.
Investigative ophthalmology & visual science, 1996Co-Authors: Chuman T, A Sawada, Nobuhisa Nao-i, Ryuichi Yamamoto, Hideki Chuman, Akihiko WadaAbstract:Purpose. The rabbit Iris Sphincter Muscle is innervated by cholinergic and tachykinergic nerves that regulate its tone. To clarify the involvement of nitric oxide (NO) in the postsynaptic regulation of the rabbit Iris Sphincter Muscle tone, the authors examined the effects of NOrelated agents on the cholinergic contraction induced by carbamylcholine (carbachol) and the tachykinergic contraction induced by neurokinin A. Methods. The motor activity of the ring-shaped rabbit Iris Sphincter Muscle was measured isometrically. Sodium nitroprusside (SNP, a NO donor) was administered between the first and second administrations of carbachol and neurokinin A, each of which induced sustained contraction. The effects of carboxy-2-phenyl-4,4,5,5,-tetramethyl-imidazoline-l-oxyl-3-oxide (carboxy-PTIO, a scavenger of NO radicals), N c '-monomethyl-Lrarginine (L-NAME, an inhibitor of NO formation from L-arginine), and methylene blue (an inhibitor of soluble guanylate cyclase) on contractions induced by carbachol and neurokinin A also were studied. Cyclic guanosine monophosphate (GMP) content in the Muscle was determined by radioimmunoassay. Results. Sodium nitroprusside inhibited carbachol-induced contractions of the Iris Sphincter Muscle in a concentration-dependent manner but had no effect on neurokinin A-induced Muscle contractions. Carboxy-PTIO and methylene blue significandy diminished the inhibitory effect of SNP on carbachol-induced contractions. L^NAME had no effect on contractions induced by either carbachol or neurokinin A. Sodium nitroprusside alone increased cyclic GMP accumulation in a concentration-dependent manner. Conclusions. This study showed that SNP inhibited cholinergic contractions mainly through a cyclic GMP-dependent mechanism but did not affect the tachykinergic contractions, indicating that cholinergic contraction is NO sensitive, whereas tachykinergic contraction is NO insensitive. These findings suggest that in rabbits, die cholinergic and tachykinergic responses have distinct features for the fine adjustment of the Iris Sphincter Muscle tone. Invest Ophthalmol Vis Sci. 1996;37:1437-1443. JMitric oxide (NO) is a labile free radical and is formed by NO synthase (NOS) from L-arginine as a
Akihiko Wada - One of the best experts on this subject based on the ideXlab platform.
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Relaxant effect of adrenomedullin on bovine isolated Iris Sphincter Muscle under resting conditions.
Clinical and experimental pharmacology & physiology, 2005Co-Authors: Y Uchikawa, Hideyuki Kobayashi, Akihiko Wada, M Okano, A Sawada, Y Asada, Nobuhisa Nao-i, Masamichi Ohkura, Naoko Tanaka, Ryuichi YamamotoAbstract:1. The mechanisms involved in the fine adjustment of Iris Sphincter Muscle tone are largely unknown. The aim of the present study was to clarify the effects of adrenomedullin on the resting tension of the bovine isolated Iris Sphincter Muscle. 2. The motor activity of the bovine isolated Iris Sphincter Muscle was measured isometrically. The effects of adrenomedullin on resting tension were analysed in the presence of indomethacin. The presence of adrenomedullin mRNA in the preparation was determined by reverse transcription-polymerase chain reaction. Immunolabelling for adrenomedullin was also performed. 3. Adrenomedullin significantly decreased the resting tension of the Muscle. The relaxant effect of adrenomedullin was significantly inhibited by adrenomedullin (22-52), a putative antagonist for the adrenomedullin receptor, or calcitonin gene-related peptide (CGRP) (8-37), a putative antagonist for the CGRP1 receptor. The relaxant effect was almost completely blocked by a combination of adrenomedullin (22-52) and CGRP (8-37). 4. The relaxant effect of adrenomedullin was also significantly diminished by 2',5'-dideoxyadenosine, an inhibitor of adenylate cyclase, N(G)-nitro-L-arginine, an inhibitor of nitric oxide synthesis, or 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, an inhibitor of soluble guanylate cyclase. 5. Reverse transcription-polymerase chain reaction analysis showed that adrenomedullin mRNA was expressed in the Muscle strip. Immunopositive staining for adrenomedullin was detected in blood vessel cells and in the Iris Sphincter Muscle cells. 6. These results suggest that adrenomedullin may be an autocrine and paracrine regulator of the resting tension of the Iris Sphincter Muscle. Its biological effects may be due to the direct involvement of adrenomedullin receptors and also to the stimulation of CGRP1 receptors. The stimulation of these receptors by the peptide leads to the activation of adenylate cyclase and soluble guanylate cyclase and subsequent relaxation of the Muscle strip.
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Different responsiveness to nitric oxide-cyclic guanosine monophosphate pathway in cholinergic and tachykinergic contractions of the rabbit Iris Sphincter Muscle.
Investigative ophthalmology & visual science, 1997Co-Authors: Hideki Chuman, Hideyuki Kobayashi, A Sawada, Nobuhisa Nao-i, Ryuichi Yamamoto, Chuman T, Akihiko WadaAbstract:Purpose. In the rabbit Iris Sphincter Muscle, sodium nitroprusside (SNP), a nitric oxide (NO) donor, inhibits cholinergic contraction but does not affect tachykinergic contraction in vitro. The objectives of the current study were to clarify the mechanism for the different responsiveness to NO in cholinergic and tachykinergic muscular contractions, and to examine whether the mechanism for NO-induced inhibition of cholinergic muscular contraction is operative in vivo. Methods. Iris Sphincter Muscle was dissected from the rabbit eye pretreated with or without endotoxin (lipopolysaccharide, LPS) in vivo. Cyclic guanosine monophosphate (cGMP) content in the Iris Sphincter Muscle was determined by radioimmunoassay. The motor activity of the ringshaped Iris Sphincter Muscle was measured isometrically. Sodium nitroprusside, carboxy-2-phenyl-4,4,5,5,-tetramethyl-imidazoline-1-oxyl-3-oxide (C-PTIO, a scavenger of NO radicals), and 8-bromo cGMP (a permeable cGMP analogue) were administered between the first and second administrations of carbachol and neurokinin A, both of which had caused sustained contraction in the Iris Sphincter Muscle. Results. Sodium nitroprusside inhibited the contraction of the Iris Sphincter Muscle caused by carbachol but had no effect on the contraction caused by neurokinin A Application of C-PTIO significantly reduced SNP-induced cGMP accumulation in the Muscle, as well as the SNP-induced inhibition of muscular contraction caused by carbachol. Neither carbachol nor neurokinin A influenced SNP-induced cGMP accumulation in the Muscle. Induction of 8-bromo-cGMP significantly diminished the muscular contraction caused by carbachol but not that caused by neurokinin A. In vivo pretreatment of the eye with LPS increased, in a time-dependent manner, the cGMP accumulation in the Iris Sphincter Muscle, which was significantly inhibited by pretreatment of N G -nitro-L-arginine methyl ester (an inhibitor of NO synthesis) in vivo. Conclusions. These results demonstrate that in rabbits the increase in cGMP accumulation induced by NO in the Iris Sphincter Muscle is involved in the cholinergic contraction but not in the tachykinergic contraction, suggesting that different sensitivities to cGMP are essential for the different responsiveness to NO. Furthermore, the results of this study showed that the NO-cGMP pathway is operative in vivo and regulates Iris Sphincter Muscle tone, at least when the eyes are infected with bacteria.
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Nitric oxide-sensitive and -insensitive contractions of the isolated rabbit Iris Sphincter Muscle.
Investigative ophthalmology & visual science, 1996Co-Authors: Chuman T, A Sawada, Nobuhisa Nao-i, Ryuichi Yamamoto, Hideki Chuman, Akihiko WadaAbstract:Purpose. The rabbit Iris Sphincter Muscle is innervated by cholinergic and tachykinergic nerves that regulate its tone. To clarify the involvement of nitric oxide (NO) in the postsynaptic regulation of the rabbit Iris Sphincter Muscle tone, the authors examined the effects of NOrelated agents on the cholinergic contraction induced by carbamylcholine (carbachol) and the tachykinergic contraction induced by neurokinin A. Methods. The motor activity of the ring-shaped rabbit Iris Sphincter Muscle was measured isometrically. Sodium nitroprusside (SNP, a NO donor) was administered between the first and second administrations of carbachol and neurokinin A, each of which induced sustained contraction. The effects of carboxy-2-phenyl-4,4,5,5,-tetramethyl-imidazoline-l-oxyl-3-oxide (carboxy-PTIO, a scavenger of NO radicals), N c '-monomethyl-Lrarginine (L-NAME, an inhibitor of NO formation from L-arginine), and methylene blue (an inhibitor of soluble guanylate cyclase) on contractions induced by carbachol and neurokinin A also were studied. Cyclic guanosine monophosphate (GMP) content in the Muscle was determined by radioimmunoassay. Results. Sodium nitroprusside inhibited carbachol-induced contractions of the Iris Sphincter Muscle in a concentration-dependent manner but had no effect on neurokinin A-induced Muscle contractions. Carboxy-PTIO and methylene blue significandy diminished the inhibitory effect of SNP on carbachol-induced contractions. L^NAME had no effect on contractions induced by either carbachol or neurokinin A. Sodium nitroprusside alone increased cyclic GMP accumulation in a concentration-dependent manner. Conclusions. This study showed that SNP inhibited cholinergic contractions mainly through a cyclic GMP-dependent mechanism but did not affect the tachykinergic contractions, indicating that cholinergic contraction is NO sensitive, whereas tachykinergic contraction is NO insensitive. These findings suggest that in rabbits, die cholinergic and tachykinergic responses have distinct features for the fine adjustment of the Iris Sphincter Muscle tone. Invest Ophthalmol Vis Sci. 1996;37:1437-1443. JMitric oxide (NO) is a labile free radical and is formed by NO synthase (NOS) from L-arginine as a
A.f. Leite-moreira - One of the best experts on this subject based on the ideXlab platform.
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Urocortin2 relaxes the Iris Sphincter Muscle
Acta Ophthalmologica, 2009Co-Authors: A Rocha De Sousa, Marta Tavares-silva, Sara Fonseca, S Cardoso, A.f. Leite-moreiraAbstract:Purpose Urocortin 2 (Ucn2) is an endogenous peptide of the corticotropin releasing factor family which presents many physiological effects at different levels in the organism. At the ocular level, Ucn2 is expressed in the retinal pigmented epithelium and has a protective effect in retinal degeneration pos-ischemia. Also in the eye, Ucn2 has a vasodilator effect in the retinal circulation, specifically, in retinal resistance arterioles. This effect is diminished in diabetic mice. However, it has not been described yet the role of Ucn 2 in the neurohumoral regulation of the anterior segment of the eye. Our purpose is to characterize the effect of Ucn2 and its sub-cellular pathways on Iris Sphincter Muscle contraction. Methods We tested the effect of increasing concentrations of Ucn2 (10-10-10-6 M) on carbacol-precontracted (10-6 M) rabbit Iris Sphincter Muscles (n = 9). The effect of Ucn2 was also tested in the presence of: (i) Nω-nitro-L-Arginine (L-NA; 10-5 M; n = 13) and (ii) indomethacin (10-5 M; n = 7). Results Ucn2 promoted a concentration-dependent decrease on active tension of the precontracted Iris Sphincter Muscles, with maximal effect at 10-6M (12,9 ± 4,1%). This effect was blunted with indomethacin (2,1 ± 4,4%) and with L-NA(2,17 ± 5,79%) . Conclusion Ucn2 promotes the relaxation of Iris Sphincter Muscle. This effect is mediated by prostaglandins and it is also dependent on nitric oxide production. As observed Ucn2 is a new neurohumoral factor that modulates the relaxation of Iris Sphincter Muscle.
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ETB2 Receptor Subtype Stimulation Relaxes the Iris Sphincter Muscle
Physiological research, 2008Co-Authors: Amândio Rocha-sousa, J. Saraiva, M. Amaral, P Alves-faria, Fernando Falcão-reis, A.f. Leite-moreiraAbstract:Effects of ET(B) receptor stimulation and its subcellular pathways were evaluated in carbachol pre-contracted rabbit Iris Sphincter Muscles (n=51). ET(B) stimulation with sarafotoxin (SRTX-c; 10(-10)-10(-6) M) was tested in the absence (n=7) or presence of 10(-5) M of: BQ-788 (ET(B2) receptor antagonist; n=6), L-NA (NOS inhibitor; n=7) or indomethacin (cyclooxygenase inhibitor; n=10). Effects of ET(B) stimulation by endothelin-1 (ET-1; 10(-10)-10(-7) M) in the presence of an ET(A) receptor antagonist (BQ-123; 10(-5) M; n=7) and of ET(B1) stimulation by IRL-1620 (10(-10)-10(-7) M; n=7) were also tested. Finally, the effects of SRTX-c (10(-9)-10(-7) M) in electric field stimulation (EFS) contraction were evaluated (n=7). ET(B) receptor stimulation by SRTX-c or ET-1 in presence of BQ-123 promoted a concentration-dependent relaxation of the rabbit Iris Sphincter Muscle by 10.8+/-2.0% and 9.4+/-1.8%, respectively. This effect was blocked by BQ-788 (-2.3+/-2.0 %), L-NA (4.5+/-2.3 %) or indomethacin (2.3+/-2.9 %). Selective ET(B1) stimulation by IRL-1620 did not relax the Iris Sphincter Muscle (0.9+/-5.4 %). EFS elicited contraction was not altered by SRTX-c. In conclusion, ET(B) receptor stimulation relaxes the carbachol precontracted Iris Sphincter Muscle, an effect that is mediated by the ET(B2) receptor subtype, through NO and the release of prostaglandins.
