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Atrial natriuretic peptide (ANP) acts via specific binding sites on cGMP system of rat pancreatic islets without affecting insulin release

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Summary

Atrial natriuretic peptide (ANP) has been shown to increase plasma insulin levels in vivo and to act on various target cells as a potent stimulator of the cGMP system. It has, therefore, been investigated whether ANP has a direct insulinotropic effect mediated by specific binding sites and by affecting the cGMP system in isolated rat pancreatic islets. Unlabelled ANP inhibited 125-ANP binding in a concentration-related manner (K d1 and K d2 = 0.02 and 11.2 nM, B max1 and B max2 = 0.0147 and 0.0328 pmoles per 1 mg protein). ANP was able to augment cGMP levels in islets, but was not able to enhance insulin secretion at various glucose concentrations. Since the role of cGMP for the glucose-mediated insulin release is controversial, in addition to ANP M&B 22,948 (a cGMP phosphodiesterase inhibitor) was investigated to evaluate the possible role of cGMP for insulin release more precisely. Like ANP M&B 22,948 increased cGMP levels but did not affect insulin release. The data indicate no direct insulinotropic effect of ANP, although ANP binding sites are present on rat pancreatic islets and question the claimed role of cGMP for insulin secretion in general. Therefore, the recently observed in vivo elevation of plasma insulin levels in response to ANP is rather an indirect than a direct effect.

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Authors and Affiliations

  1. Department of Pharmacology, Institute of Pharmaceutical Science, Auf der Morgenstelle B, D-7400, Tübingen, Federal Republic of Germany

    Eugen J. Verspohl & Hermann P. T. Ammon

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  1. Eugen J. Verspohl
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  2. Hermann P. T. Ammon
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Verspohl, E.J., Ammon, H.P.T. Atrial natriuretic peptide (ANP) acts via specific binding sites on cGMP system of rat pancreatic islets without affecting insulin release. Naunyn-Schmiedeberg's Arch Pharmacol 339, 348–353 (1989). https://doi.org/10.1007/BF00173590

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  • DOI: https://doi.org/10.1007/BF00173590

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