AJP - Endocrinology and Metabolism, Vol 251, Issue 4 416-E421, Copyright © 1986 by American Physiological Society
Potentiating synergism between adenosine diphosphate or triphosphate and acetylcholine on insulin secretion
G. Bertrand, J. Chapal and M. M. Loubatieres-Mariani
The interaction between adenosine di- or triphosphate (ADP or ATP) and
acetylcholine (ACh) was studied on insulin secretion. The experiments were
performed on the isolated perfused rat pancreas, in the presence of a
physiological nonstimulating glucose concentration (5.5 mM). ADP or ATP
(1.65 microM) and ACh (0.05 microM) elicited a comparable peak of insulin
secretion. When either ATP or ADP was simultaneously infused with ACh,
insulin secretory response was significantly higher than the sum of the
responses of each agonist applied separately. Similar effects were obtained
with stable structural analogues of ATP and ADP (adenylimidodiphosphate,
AMP-PNP, and alpha, beta-methyleneadenosine 5'-diphosphate, alpha,
beta-methylene ADP) whether they acted alone or in combination with ACh. In
contrast, adenosine was ineffective. Furthermore, the study of combined
half doses of ATP (or ADP) and ACh allowed us to establish a potentiating
synergism between both agonists. These data indicate a potentiating
synergism on the beta-cell between ACh and ATP or ADP, the substances
acting, respectively, via muscarinic cholinergic receptors and purinergic
P2 receptors. So, ATP and ADP by activating P2 receptors could be involved
in the parasympathetic control of insulin secretion.
