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Eric W. Roubos - One of the best experts on this subject based on the ideXlab platform.
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Action of stimulatory and inhibitory α-MSH secretagogues on spontaneous calcium oscillations in melanotrope cells of Xenopus laevis
Pflügers Archiv, 1994Co-Authors: Wim J. J. M. Scheenen, Bruce G. Jenks, Peter H. G. M. Willems, Eric W. RoubosAbstract:The secretion of α -melanophore-stimulating hormone ( α -MSH) from melanotrope cells in the pituitary gland of Xenopus laevis is regulated by various neural factors, both classical neurotransmitters and neuroPeptides. The majority of these cells (80%) display spontaneous Ca^2+ oscillations. In order to gain a better understanding of the external regulation of intracellular Ca^2+ ([Ca^2+]_i) in the melanotrope cell, we have examined the action of well known α -MSH secretagogues on the Ca^2+ oscillations. It is shown that all secretagogues tested also control the oscillatory state of Xenopus melanotropes, that is, the secreto-inhibitors dopamine, isoguvacine ( γ -aminobutyric acid, GABA_A agonist), baclofen (GABA_B agonist) and neuroPeptide Y evoked a rapid quenching of the spontaneous Ca^2+ oscillations, whereas the secreto-stimulant sauvagine, an Amphibian Peptide related to corticotropin releasing hormone, induced oscillatory activity in non-oscillating cells. Supporting argument is given for the idea that the regulation of Ca^2+ oscillations is a focal point in the regulation of secretory activity of melanotrope cells. There was considerable heterogeneity among melanotrope cells in the threshold of their Ca^2+ response to secretagogue treatment. This heterogeneity may be the basis for melanotrope cell recruitment observed during physiological adaptations of the animal to the light intensity of its background.
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Action of stimulatory and inhibitory alpha-MSH secretagogues on spontaneous calcium oscillations in melanotrope cells of Xenopus laevis.
Pflugers Archiv : European journal of physiology, 1994Co-Authors: Wim J. J. M. Scheenen, Bruce G. Jenks, Peter H. G. M. Willems, Eric W. RoubosAbstract:The secretion of alpha-melanophore-stimulating hormone (alpha-MSH) from melanotrope cells in the pituitary gland of Xenopus laevis is regulated by various neural factors, both classical neurotransmitters and neuroPeptides. The majority of these cells (80%) display spontaneous Ca2+ oscillations. In order to gain a better understanding of the external regulation of intracellular Ca2+ ([Ca2+]i) in the melanotrope cell, we have examined the action of well known alpha-MSH secretagogues on the Ca2+ oscillations. It is shown that all secretagogues tested also control the oscillatory state of Xenopus melanotropes, that is, the secreto-inhibitors dopamine, isoguvacine (gamma-aminobutyric acid, GABAA agonist), baclofen (GABAB agonist) and neuroPeptide Y evoked a rapid quenching of the spontaneous Ca2+ oscillations, whereas the secreto-stimulant sauvagine, an Amphibian Peptide related to corticotropin releasing hormone, induced oscillatory activity in non-oscillating cells. Supporting argument is given for the idea that the regulation of Ca2+ oscillations is a focal point in the regulation of secretory activity of melanotrope cells. There was considerable heterogeneity among melanotrope cells in the threshold of their Ca2+ response to secretagogue treatment. This heterogeneity may be the basis for melanotrope cell recruitment observed during physiological adaptations of the animal to the light intensity of its background.
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Dynamics of cyclic-AMP efflux in relation to α-MSH secretion from melanotrope cells of Xenopus laevis
Life sciences, 1992Co-Authors: Harry P. De Koning, Bruce G. Jenks, Bertrand Huchedé, Eric W. RoubosAbstract:An important factor in regulating secretion from endocrine cells is the cytoplasmic concentration of cyclic-AMP. Many regulatory substances are known to either stimulate or inhibit the production of this second messenger through activation of their receptors. In the present study, we have monitored changes in cyclic-AMP efflux from melanotrope cells of Xenopus laevis in response to established neurochemical regulators of α-MSH secretion. In vitro superfusion of neurointermediate lobes allows for a dynamic recording of cyclic-AMP production in relation to hormone secretion. Unlike α-MSH secretion, the efflux of cyclic-AMP was not dependent on the concentration of extracellular calcium, indicating that hormone release and cyclic-AMP efflux are mediated by different mechanisms. The phosphodiesterase inhibitor IBMX and the adenylate cyclase activator forskolin stimulated cyclic-AMP efflux, but had no stimulatory effect on α-MSH release. This indicates that an increase in cyclic-AMP production in melanotrope cells is not necessarily accompanied by an increase in the rate of α-MSH release. Corticotropin-releasing factor stimulated cyclic-AMP efflux with dynamics similar to that induced by the Amphibian Peptide sauvagine. Dopamine and the GABAB receptor agonist baclofen both inhibited cyclic-AMP efflux and α-MSH release, with similar dynamics of inhibition and similar dose-response relationships. It is proposed that an inhibition of cyclic-AMP efflux is coupled to an inhibition of α-MSH secretion.
John H. Bowie - One of the best experts on this subject based on the ideXlab platform.
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The membrane-active Amphibian Peptide caerin 1.8 inhibits fibril formation of amyloid β1-42.
Peptides, 2015Co-Authors: Yanqin Liu, Tianfang Wang, Antonio N. Calabrese, John A. Carver, Scott F. Cummins, John H. BowieAbstract:The Amphibian host-defense Peptide caerin 1.8 [(1)GLFKVLGSV(10)AKHLLPHVVP(20)VIAEKL(NH2)] inhibits fibril formation of amyloid β 1-42 [(1)DAEFRHDSG(10)YEVHHQKLVF(20)FAEDVGSNKG(30)AIIGLMVGGV(40)VIA] [Aβ42] (the major precursor of the extracellular fibrillar deposits of Alzheimer's disease). Some truncated forms of caerin 1.8 also inhibit fibril formation of Aβ42. For example, caerin 1.8 (1-13) [(1)GLFKVLGSV(10)AKHL(NH2) and caerin 1.8 (22-25) [KVLGSV(10)AKHLLPHVVP(20)VIAEKL(NH2)] show 85% and 75% respectively of the inhibition activity of the parent caerin 1.8. The synthetic Peptide KLVFFKKKKKK is a known inhibitor of Aβ42 fibril formation, and was used as a standard in this study. Caerin 1.8 is the more effective fibril inhibitor. IC50 values (± 15%) are caerin 1.8 (75 μM) and KLVFFKKKKKK (370 μM). MALDI mass spectrometry shows the presence of a small peak corresponding to a protonated 1:1 adduct [caerin 1.8/Aβ42]H(+). Molecular dynamics simulation suggests that both hydrogen bonding and hydrophobic interactions between Aβ42 and caerin 1.8 facilitate the formation of a 1:1 complex in water. Fibril formation from Aβ42 has been proposed to be based around the (16)KLVF(20)F region of Aβ42; this region in the 1:1 complex is partially blocked from attachment of a further molecule of Aβ42.
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The investigation of membrane binding by Amphibian Peptide agonists of CCK2R using 31P and 2H solid-state NMR
Peptides, 2014Co-Authors: Patrick J. Sherman, Frances Separovic, John H. BowieAbstract:Abstract It has been proposed that some neuroPeptides may be anchored to the cell membranes prior to attaching to the adjacent active sites of transmembrane receptors. The three Amphibian skin neuroPeptides signiferin 1 [RL CIPYIIPC (OH)] (smooth muscle active and immunomodulator), riparin 1.1 [[RL CIPVIFPC (OH)] (immunomodulator) and rothein 1 [SVSNIPESIGF(OH)] (immunomodulator) act via CCK2 transmembrane receptors. A combination of 31P and 2H solid state NMR studies of each of these three Peptides in eukaryotic phospholipid models at 25 °C shows that rothein 1 does not interact with the membrane at all. In contrast, both of the cyclic disulfides signiferin 1 and riparin 1.1 interact with phospholipid head groups and partially penetrate into the upper leaflet of the model bilayer, but to different extents. These interactions are not sufficiently effective to cause disruption of the lipid bilayer since the Peptides are not antimicrobial, anticancer, antifungal nor active against enveloped viruses.
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Binding studies of nNOS-active Amphibian Peptides and Ca2+ calmodulin, using negative ion electrospray ionisation mass spectrometry.
Rapid Communications in Mass Spectrometry, 2008Co-Authors: Tara L. Pukala, Thitima Urathamakul, Stephen J. Watt, Jennifer L. Beck, Rebecca J. Jackway, John H. BowieAbstract:Amphibian Peptides which inhibit the formation of nitric oxide by neuronal nitric oxide synthase (nNOS) do so by binding to the protein cofactor, Ca 2+ calmodulin (Ca 2+ CaM). Complex formation between active Peptides and Ca 2+ CaM has been demonstrated by negative ion electrospray ionisation mass spectrometry using an aqueous ammonium acetate buffer system. In all cases studied, the assemblies are formed with a 1:1:4 calmodulin/Peptide/Ca 2+ stoichiometry. In contrast, the complex involving the 20-residue binding domain of the plasma Ca 2+ pump C20W (LRRGQILWFRGLN-RIQTQIK-OH) with CaM has been shown by previous two-dimensional nuclear magnetic resonance (2D NMR) studies to involve complexation of the C-terminal end of CaM. Under identical conditions to those used for the Amphibian Peptide study, the ESI complex between C20W and CaM shows specific 1:1:2 stoichiometry. Since complex formation with the studied Amphibian Peptides requires Ca 2+ CaM to contain its full complement of four Ca 2+ ions, this indicates that the Amphibian Peptides require both ends of the CaM to effect complex formation. Charge-state analysis and an H/D exchange experiment (with caerin 1.8) suggest that complexation involves Ca 2+ CaM undergoing a conformational change to a more compact structure.
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Backbone cleavages of [M − H]− anions of Peptides. Cyclisation of citropin 1 Peptides involving reactions between the C‐terminal [CONH]− residue and backbone amide carbonyl groups. A new type of β cleavage: a joint experimental and theoretical study
Rapid Communications in Mass Spectrometry, 2002Co-Authors: Craig S. Brinkworth, John H. BowieAbstract:This paper reports the study of backbone cleavages in the collision-induced negative-ion mass spectra of the [M - H](-) anions of some synthetic modifications of the bioactive Amphibian Peptide citropin 1 (GLFDVIKKVASVIGGL-NH(2)). The Peptides chosen for study contain no amino acid residues which could effect facile side-chain cleavage, i.e. Ser (-CH(2)O, side-chain cleavage) and Asp (-H(2)O) are replaced by Ala or Lys. We expected that such Peptides should exhibit standard and pronounced peaks due to alpha cleavage ions (and to a lesser extent beta cleavage ions) in their collision-induced negative-ion spectra. This expectation was realised, but the spectra also contained peaks formed by a new series of cleavage anions. These are produced following cyclisation of the C-terminal CONH(-) moiety at carbonyl functions of amide groups along the Peptide backbone; effectively transferring the NH of the C-terminal CONH(-) group to other amino acid residues. We have called the product anions of these processes beta' ions, in order to distinguish them from standard beta ions. Some beta' ions also fragment directly to some other beta' ions of smaller mass. The reaction coordinates of alpha,beta and beta' backbone processes have been calculated at the HF/6-31G*//AM1 level theory for simple model systems. The initial cyclisation step of the beta' sequence is barrierless and exothermic. Subsequent steps have a maximum barrier of +40 kcal mol(-1), with the overall reaction being endothermic by some 30 kcal mol(-1) at the level of theory used. These calculations take no account of the complexity of the conformationally flexible Peptide system, and it is surprising that each of the two reacting centres can 'find' each other in such a large system.
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Amphibian Peptides that inhibit neuronal nitric oxide synthase the isolation of lesueurin from the skin secretion of the australian stony creek frog litoria lesueuri
FEBS Journal, 2002Co-Authors: Jason Doyle, Craig S. Brinkworth, John H. Bowie, Lyndon E Llewellyn, Kate L Wegener, Tomas Rozek, Paul A Wabnitz, John C Wallace, Michael J TylerAbstract:Two neuroPeptides have been isolated and identified from the secretions of the skin glands of the Stony Creek Frog Litoria lesueuri. The first of these, the known neuroPeptide caerulein 1.1, is a common constituent of anuran skin secretions, and has the sequence pEQY(SO3)TGWMDF-NH2. This neuroPeptide is smooth muscle active, an analgaesic more potent than morphine and is also thought to be a␣hormone. The second neuroPeptide, a new Peptide, has been named lesueurin and has the primary structure GLLDILKKVGKVA-NH2. Lesueurin shows no significant antibiotic or anticancer activity, but inhibits the formation of the ubiquitious chemical messenger nitric oxide from neuronal nitric oxide synthase (nNOS) at IC50 (16.2 µm), and is the first Amphibian Peptide reported to show inhibition of nNOS. As a consequence of this activity, we have tested other Peptides previously isolated from Australian Amphibians for nNOS inhibition. There are three groups of Peptides that inhibit nNOS (IC50 at µm concentrations): these are (a) the citropin/aurein type Peptides (of which lesueurin is a member), e.g. citropin 1.1 (GLFDVIKKVASVIGGL-NH2) (8.2 µm); (b) the frenatin type Peptides, e.g. frenatin 3 (GLMSVLGHAVGNVLGGLFKPK-OH) (6.8 µm); and (c) the caerin 1 Peptides, e.g. caerin 1.8 (GLFGVLGSIAKHLLPHVVPVIAEKL-NH2) (1.7 µm). From Lineweaver–Burk plots, the mechanism of inhibition is revealed as noncompetitive with respect to the nNOS substrate arginine. When the nNOS inhibition tests with the three Peptides outlined above were carried out in the presence of increasing concentrations of Ca2+calmodulin, the inhibition dropped by ≈ 50% in each case. In addition, these Peptides also inhibit the activity of calcineurin, another enzyme that requires the presence of the regulatory protein Ca2+ calmodulin. It is proposed that the Amphibian Peptides inhibit nNOS by interacting with Ca2+calmodulin, and as a consequence, blocks the attachment of this protein to the calmodulin domain of nNOS.
Bruce G. Jenks - One of the best experts on this subject based on the ideXlab platform.
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Action of stimulatory and inhibitory α-MSH secretagogues on spontaneous calcium oscillations in melanotrope cells of Xenopus laevis
Pflügers Archiv, 1994Co-Authors: Wim J. J. M. Scheenen, Bruce G. Jenks, Peter H. G. M. Willems, Eric W. RoubosAbstract:The secretion of α -melanophore-stimulating hormone ( α -MSH) from melanotrope cells in the pituitary gland of Xenopus laevis is regulated by various neural factors, both classical neurotransmitters and neuroPeptides. The majority of these cells (80%) display spontaneous Ca^2+ oscillations. In order to gain a better understanding of the external regulation of intracellular Ca^2+ ([Ca^2+]_i) in the melanotrope cell, we have examined the action of well known α -MSH secretagogues on the Ca^2+ oscillations. It is shown that all secretagogues tested also control the oscillatory state of Xenopus melanotropes, that is, the secreto-inhibitors dopamine, isoguvacine ( γ -aminobutyric acid, GABA_A agonist), baclofen (GABA_B agonist) and neuroPeptide Y evoked a rapid quenching of the spontaneous Ca^2+ oscillations, whereas the secreto-stimulant sauvagine, an Amphibian Peptide related to corticotropin releasing hormone, induced oscillatory activity in non-oscillating cells. Supporting argument is given for the idea that the regulation of Ca^2+ oscillations is a focal point in the regulation of secretory activity of melanotrope cells. There was considerable heterogeneity among melanotrope cells in the threshold of their Ca^2+ response to secretagogue treatment. This heterogeneity may be the basis for melanotrope cell recruitment observed during physiological adaptations of the animal to the light intensity of its background.
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Action of stimulatory and inhibitory alpha-MSH secretagogues on spontaneous calcium oscillations in melanotrope cells of Xenopus laevis.
Pflugers Archiv : European journal of physiology, 1994Co-Authors: Wim J. J. M. Scheenen, Bruce G. Jenks, Peter H. G. M. Willems, Eric W. RoubosAbstract:The secretion of alpha-melanophore-stimulating hormone (alpha-MSH) from melanotrope cells in the pituitary gland of Xenopus laevis is regulated by various neural factors, both classical neurotransmitters and neuroPeptides. The majority of these cells (80%) display spontaneous Ca2+ oscillations. In order to gain a better understanding of the external regulation of intracellular Ca2+ ([Ca2+]i) in the melanotrope cell, we have examined the action of well known alpha-MSH secretagogues on the Ca2+ oscillations. It is shown that all secretagogues tested also control the oscillatory state of Xenopus melanotropes, that is, the secreto-inhibitors dopamine, isoguvacine (gamma-aminobutyric acid, GABAA agonist), baclofen (GABAB agonist) and neuroPeptide Y evoked a rapid quenching of the spontaneous Ca2+ oscillations, whereas the secreto-stimulant sauvagine, an Amphibian Peptide related to corticotropin releasing hormone, induced oscillatory activity in non-oscillating cells. Supporting argument is given for the idea that the regulation of Ca2+ oscillations is a focal point in the regulation of secretory activity of melanotrope cells. There was considerable heterogeneity among melanotrope cells in the threshold of their Ca2+ response to secretagogue treatment. This heterogeneity may be the basis for melanotrope cell recruitment observed during physiological adaptations of the animal to the light intensity of its background.
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Dynamics of cyclic-AMP efflux in relation to α-MSH secretion from melanotrope cells of Xenopus laevis
Life sciences, 1992Co-Authors: Harry P. De Koning, Bruce G. Jenks, Bertrand Huchedé, Eric W. RoubosAbstract:An important factor in regulating secretion from endocrine cells is the cytoplasmic concentration of cyclic-AMP. Many regulatory substances are known to either stimulate or inhibit the production of this second messenger through activation of their receptors. In the present study, we have monitored changes in cyclic-AMP efflux from melanotrope cells of Xenopus laevis in response to established neurochemical regulators of α-MSH secretion. In vitro superfusion of neurointermediate lobes allows for a dynamic recording of cyclic-AMP production in relation to hormone secretion. Unlike α-MSH secretion, the efflux of cyclic-AMP was not dependent on the concentration of extracellular calcium, indicating that hormone release and cyclic-AMP efflux are mediated by different mechanisms. The phosphodiesterase inhibitor IBMX and the adenylate cyclase activator forskolin stimulated cyclic-AMP efflux, but had no stimulatory effect on α-MSH release. This indicates that an increase in cyclic-AMP production in melanotrope cells is not necessarily accompanied by an increase in the rate of α-MSH release. Corticotropin-releasing factor stimulated cyclic-AMP efflux with dynamics similar to that induced by the Amphibian Peptide sauvagine. Dopamine and the GABAB receptor agonist baclofen both inhibited cyclic-AMP efflux and α-MSH release, with similar dynamics of inhibition and similar dose-response relationships. It is proposed that an inhibition of cyclic-AMP efflux is coupled to an inhibition of α-MSH secretion.
Sami I. Said - One of the best experts on this subject based on the ideXlab platform.
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Small-cell lung carcinoma: inhibition of proliferation by vasoactive intestinal Peptide and helodermin and enhancement of inhibition by anti-bombesin antibody.
Life sciences, 1993Co-Authors: Kaname Maruno, Sami I. SaidAbstract:Abstract Small-cell lung cancer (SCLC) is a common and highly fatal malignancy for which there is no satisfactory treatment. The Amphibian Peptide bombesin and its mammalian counterpart, gastrin-releasing Peptide, serve as autocrine growth factors for the SCLC cells, but little is known about endogenous substances that inhibit the growth and proliferation of these tumor cells. We report that the neuroPeptide vasoactive intestinal Peptide (VIP) markedly inhibits the growth and multiplication of SCLC cell lines NCI-H345 and NCI-H69, and that the closely related Peptide helodermin inhibits the proliferation of NCI-H345 cells with even higher efficacy. In the latter cells, the inhibition by VIP and isobutyl methyl xanthine paralleled their ability to stimulate cyclic adenosine monophosphate production within the cells. The Peptide-induced suppression of SCLC proliferation is enhanced in the presence of an anti-bombesin monoclonal antibody. The anti-mitogenic activities of VIP and helodermin, and their enhancement by anti-bombesin antibody, offer the potential for a new approach to the pharmacologic control of SCLC.
Wim J. J. M. Scheenen - One of the best experts on this subject based on the ideXlab platform.
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Action of stimulatory and inhibitory α-MSH secretagogues on spontaneous calcium oscillations in melanotrope cells of Xenopus laevis
Pflügers Archiv, 1994Co-Authors: Wim J. J. M. Scheenen, Bruce G. Jenks, Peter H. G. M. Willems, Eric W. RoubosAbstract:The secretion of α -melanophore-stimulating hormone ( α -MSH) from melanotrope cells in the pituitary gland of Xenopus laevis is regulated by various neural factors, both classical neurotransmitters and neuroPeptides. The majority of these cells (80%) display spontaneous Ca^2+ oscillations. In order to gain a better understanding of the external regulation of intracellular Ca^2+ ([Ca^2+]_i) in the melanotrope cell, we have examined the action of well known α -MSH secretagogues on the Ca^2+ oscillations. It is shown that all secretagogues tested also control the oscillatory state of Xenopus melanotropes, that is, the secreto-inhibitors dopamine, isoguvacine ( γ -aminobutyric acid, GABA_A agonist), baclofen (GABA_B agonist) and neuroPeptide Y evoked a rapid quenching of the spontaneous Ca^2+ oscillations, whereas the secreto-stimulant sauvagine, an Amphibian Peptide related to corticotropin releasing hormone, induced oscillatory activity in non-oscillating cells. Supporting argument is given for the idea that the regulation of Ca^2+ oscillations is a focal point in the regulation of secretory activity of melanotrope cells. There was considerable heterogeneity among melanotrope cells in the threshold of their Ca^2+ response to secretagogue treatment. This heterogeneity may be the basis for melanotrope cell recruitment observed during physiological adaptations of the animal to the light intensity of its background.
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Action of stimulatory and inhibitory alpha-MSH secretagogues on spontaneous calcium oscillations in melanotrope cells of Xenopus laevis.
Pflugers Archiv : European journal of physiology, 1994Co-Authors: Wim J. J. M. Scheenen, Bruce G. Jenks, Peter H. G. M. Willems, Eric W. RoubosAbstract:The secretion of alpha-melanophore-stimulating hormone (alpha-MSH) from melanotrope cells in the pituitary gland of Xenopus laevis is regulated by various neural factors, both classical neurotransmitters and neuroPeptides. The majority of these cells (80%) display spontaneous Ca2+ oscillations. In order to gain a better understanding of the external regulation of intracellular Ca2+ ([Ca2+]i) in the melanotrope cell, we have examined the action of well known alpha-MSH secretagogues on the Ca2+ oscillations. It is shown that all secretagogues tested also control the oscillatory state of Xenopus melanotropes, that is, the secreto-inhibitors dopamine, isoguvacine (gamma-aminobutyric acid, GABAA agonist), baclofen (GABAB agonist) and neuroPeptide Y evoked a rapid quenching of the spontaneous Ca2+ oscillations, whereas the secreto-stimulant sauvagine, an Amphibian Peptide related to corticotropin releasing hormone, induced oscillatory activity in non-oscillating cells. Supporting argument is given for the idea that the regulation of Ca2+ oscillations is a focal point in the regulation of secretory activity of melanotrope cells. There was considerable heterogeneity among melanotrope cells in the threshold of their Ca2+ response to secretagogue treatment. This heterogeneity may be the basis for melanotrope cell recruitment observed during physiological adaptations of the animal to the light intensity of its background.
