Elsevier

Peptides

Volume 5, Issue 2, March–April 1984, Pages 379-383
Peptides

Release and functional role
Adrenergic versus VIPergic control of cyclic AMP in human colonic crypts

https://doi.org/10.1016/0196-9781(84)90238-9Get rights and content

Abstract

The actions of catecholamines on VIP-induced cyclic AMP is studied in human colon. We show that: (1) Epinephrine in the 10−7–10−3 M concentration range (ED50=11.10−6M) inhibits VIP-induced cyclic AMP rise in isolated colonic epithelial cells; the maximal inhibition reaches 30% of VIP effect; epinephrine alters the efficacy of the peptide and does not modify its potency; epinephrine also reduces the basal cyclic AMP level. (2) The inhibition is found with other α adrenergic agonists with the order of potencies epinephrine > norepinephrine > phenylephrine. Clonidine has a poor intrinsic activity but antagonizes the action of epinephrine. (3) The inhibition of VIP action by epinephrine is reversed by the α antagonists dihydroergotamine, phentolamine and the α2 antagonist yohimbine, while unaffected by the β antagonist propranolol and the α1 antagonist prazosin, (4) Epinephrine inhibits VIP-stimulated adenylate cyclase activity in preparations of colonic plasma membranes. Thus catecholamines exert through an α2 adrenoreceptor a negative control on basal and VIP-stimulated cyclic AMP formation in human colon. We suggest that colonic cyclic AMP metabolism undergoes a dual control: VIPergic, activator and adrenergic, inhibitor.

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    This investigation was possible through close cooperation with the Department of Digestive Surgery directed by Professor J. Loygue, to whom we are greatly indebted. This work was supported by a grant from the Fondation pour la Recherche Médicale Française. We would like to thank Mrs. C. Rouyer-Fessard for her excellent technical assistance and Mrs. D. Lhenry for the preparation of the manuscript.

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