Electrophysiological effects of calcitonin gene‐related peptide in bull‐frog and guinea‐pig atrial myocytes.

Ono, Koji; Giles, Wayne R.

doi:10.1113/jphysiol.1991.sp018546

Cited by 25 publications

(7 citation statements)

References 50 publications

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“…These effects are believed to be due to opening of KATP channels or to direct interactions with guanine nucleotide binding proteins coupled to ion channels or to exocytotic machinery (13,27). Similarly, calcitonin-gene-related peptide (CGRP), which shares 46% sequence homology with amylin and modulates K and Ca currents in muscle and nerve (28)(29)(30)(31), reduces insulin secretion from both single rat (8 cells and islets (32,33). Although it is possible that local (3cell effects of amylin are mediated through low-affinity CGRP receptors (34), both amylin secretion from the , cell and its link to type II diabetes make it unique among peptide and hormone modulators of the l3 cell (35,36).…”

Section: Resultsmentioning

confidence: 99%

Amylin modulates beta-cell glucose sensing via effects on stimulus-secretion coupling.

Wagoner

Chen

Worley

et al. 1993

Proc. Natl. Acad. Sci. U.S.A.

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The release of insulin from the pancreatic ,B cell is dependent upon a complex interplay between stinulators and inhibitors. Recently, amylin, a peptide secreted by pancreatic ,B ceils, has been implicated in the development of type II (noninsulin dependent) diabetes through its modulation of the peripheral effects of insulin. However, the effect of amylin on insulin secretion from the .8 cell has remained controversial.It is reported here that in single ,B cells exhibiting normal glucose sensing, amylin causes membrane hyperpolarization, increases in net outward current, and reductions in insulin secretion. In contrast, in cells with abnormal glucose sensing (e.g., from db/db diabetic mice), amylin has no effect on electrical activity or secretion. Thus, amylin's effects on excitation-secretion coupling in the (8 cell of the pancreas appear to be linked to the cell's capacity for normal glucose sensing.Although the mysteries underlying the effects of glucose and other secretagogues on pancreatic ,B-cell electrical and secretory activity are rapidly unfolding, the mechanisms by which hormones and peptides modulate these activities remain unclear. Certain neuropeptides, released by nerves supplying the pancreas, decrease insulin secretion. This inhibition involves coupling between receptors and ion channels (1). In contrast to such neurotransmitters, it is not known whether and how peptides secreted from the ,B cells themselves affect insulin secretion. Amylin, a 37-aa peptide, is colocalized with insulin in 13-cell secretory granules of human islets (2) and is cosecreted with insulin. It is also the major component of pancreatic islet amyloid commonly found in the pancreases of patients with non-insulin-dependent diabetes mellitus (3). In this disease, loss of normal glucose sensing is one of the earliest defects. Although peripheral actions of amylin have been demonstrated, the influence of amylin on insulin secretion is still debated (4-7). Though the overall role ofamylin in regulating insulin secretion and in the development of diabetes may remain unclear for some time, it is critical to determine the effects of amylin on stimulussecretion coupling at the single-cell level. Thus, we have examined the effects of amylin on excitation and insulin secretion in single isolated pancreatic /3 cells that exhibit normal or abnormal glucose sensing. METHODSTo determine the effects of both glucose and amylin on membrane electrical parameters of single /8 cells, we used the nystatin perforated patch technique (8) to record membrane potentials and ion currents. Detection of insulin secretion from single 13 cells was accomplished using a sequential-cell immunoblot method (9) whereby cells are stimulated to secrete insulin into peptide-retentive immunoblot materialThe publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact. and secreted hormone is quantified by standar...

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Section: Resultsmentioning

confidence: 99%

Amylin modulates beta-cell glucose sensing via effects on stimulus-secretion coupling.

Wagoner

Chen

Worley

et al. 1993

Proc. Natl. Acad. Sci. U.S.A.

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“…To explore the ionic mechanism(s) of these CNP effects on the action potential, voltage clamp measurements of I Ca were made as described previously (50). The effects of CNP were first measured on basal (unstimulated) I Ca .…”

Section: Effects Of Cnp On I Camentioning

confidence: 99%

Inhibition of L-type Ca²⁺current by C-type natriuretic peptide in bullfrog atrial myocytes: an NPR-C-mediated effect

Rose

Lomax²,

Giles³

2003

American Journal of Physiology-Heart and Circulatory Physiology

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Single atrial myocytes were isolated from the bullfrog heart and studied under current and voltage clamp conditions to determine the electrophysiological effects of the C-type natriuretic peptide (CNP). CNP (10(-8) M) significantly shortened the action potential and reduced its peak amplitude after the application of isoproteronol (10(-7) M). In voltage clamp studies, CNP inhibited isoproteronol-stimulated L-type Ca2+ current (ICa) without any significant effect on the inward rectifier K+ current. The effects of cANF (10(-8) M), a selective agonist of the natriuretic peptide C receptor (NPR-C), were very similar to those of CNP. Moreover, HS-142-1, an antagonist of the guanylyl cyclase-linked NPR-A and NPR-B receptors did not alter the inhibitory effect of CNP on ICa. Inclusion of cAMP in the recording pipette to stimulate ICa at a point downstream from adenylyl cyclase increased ICa, but this effect was not inhibited by cANF. These results provide the first demonstration that CNP can inhibit ICa after binding to NPR-C, and suggest that this inhibition involves a decrease in adenylyl cyclase activity, which leads to reduced intracellular levels of cAMP.

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“…This corresponds well with the study of Bell and McDermott [6] who have demonstrated that the positive inotropic effect of CGRP in rat ventricular myocytes is not antagonized by the selective L-type Ca 2+ channel antagonists, diltiazem or verapamil. On the other hand, in preparations such as guinea-pig atrial myocytes, CGRP stimulates cAMP production and I Ca,L [16,23,24]. Increased cAMP levels in the presence of CGRP have been reported also in cultured neonatal rat myocardial cells [22] and in rat atria [15,29] but not in ventricles [15].…”

Section: Discussionmentioning

confidence: 93%

“…With regard to the inotropic effects conflicting results have been reported depending on the animal species and tissue studied. The positive inotropic effect in guinea-pig atrial myocytes has been attributed to the stimulation of Ca 2+ currents and adenosine 3′,5′-cyclic monophosphate (cAMP) production [16,23,24]. In rat ventricular cells a positive inotropic effect is also found, although it is insensitive to selective blockers of L-type Ca 2+ channels as well as to a cAMP antagonist [4,5,6].…”

Section: Introductionmentioning

confidence: 96%

Calcitonin gene-related peptide suppresses the transient outward current in rat ventricular myocytes

Štengl

Barták

2000

Pflügers Arch - Eur J Physiol

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The effects of calcitonin gene-related peptide (CGRP) on the transient outward current (Ito) and the L-type calcium current (ICa,L) were investigated in isolated rat ventricular cardiomyocytes using the whole-cell, patch-clamp technique. CGRP influenced neither the amplitude nor the time course of ICa,L. On the other hand, at all membrane potentials at which a significant Ito was elicited, CGRP decreased its amplitude. The effect on Ito was completely reversible and independent of membrane potential. The steady-state activation and inactivation curves of Ito were not influenced by CGRP. The time course of Ito inactivation was satisfactorily fitted by two exponentials. Both the fast and the slow time constants of inactivation were voltage independent and were not influenced by CGRP. The effect of CGRP on Ito was concentration dependent with half-maximum inhibition at 99 nM. Chelerythrine, a selective inhibitor of protein kinase C, prevented the effect of CGRP on Ito. The data indicate that CGRP suppresses Ito in a concentration-dependent, but membrane potential-independent manner and that the effect is probably mediated via a protein kinase C-dependent pathway.

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Electrophysiological effects of calcitonin gene‐related peptide in bull‐frog and guinea‐pig atrial myocytes.

Cited by 25 publications

References 50 publications

Amylin modulates beta-cell glucose sensing via effects on stimulus-secretion coupling.

Amylin modulates beta-cell glucose sensing via effects on stimulus-secretion coupling.

Inhibition of L-type Ca²⁺current by C-type natriuretic peptide in bullfrog atrial myocytes: an NPR-C-mediated effect

Calcitonin gene-related peptide suppresses the transient outward current in rat ventricular myocytes

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Electrophysiological effects of calcitonin gene‐related peptide in bull‐frog and guinea‐pig atrial myocytes.

Cited by 25 publications

References 50 publications

Amylin modulates beta-cell glucose sensing via effects on stimulus-secretion coupling.

Amylin modulates beta-cell glucose sensing via effects on stimulus-secretion coupling.

Inhibition of L-type Ca2+current by C-type natriuretic peptide in bullfrog atrial myocytes: an NPR-C-mediated effect

Calcitonin gene-related peptide suppresses the transient outward current in rat ventricular myocytes

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Inhibition of L-type Ca²⁺current by C-type natriuretic peptide in bullfrog atrial myocytes: an NPR-C-mediated effect