Islet-activating protein. A modifier of receptor-mediated regulation of rat islet adenylate cyclase.

Adenylate cyclase of the membrane-rich fraction of 24-h cultured islets was inhibited by epinephrine via alpha-adrenergic receptors. Epinephrine was inhibitory only when the enzyme was activated by GTP; the degree of inhibition was highly proportional to the degree of GTP activation. Adenylate cyclase of islets cultured with islet-activating protein (IAP), one of the pertussis toxins, was less susceptible to epinephrine inhibition. The degree of the inhibition was markedly reduced without changes in potency of the catecholamine and in GTP dependence after IAP treatment. None of the other kinetic properties of the enzyme including the affinity for substrate, sensitivity to guanine nucleotide and fluoride activation, and cholera toxin-induced modification of enzymic activity were affected by treatment of islets with IAP, suggesting that neither the catalytic nor the GTP-regulatory component of the membrane adenylate cyclase complex is the site of IAP action. Slight activation of the enzyme by glucagon or adenosine tended to be enhanced by IAP treatment. Thus, a mechanism whereby membrane receptors are linked to adenylate cyclase appears to be modified by exposure of islet cells to IAP.