Effects of vasoactive intestinal polypeptide, monoamines, prostaglandins, and 2-chloroadenosine on adenylate cyclase...

Adenylate cyclase in microvessels isolated from rat cerebral cortex was stimulated by guanine nucleotides, catecholamines, prostaglandin E1, prostaglandin E2, and 2-chloroadenosine. Catecholamine stimulation was mediated by interaction with beta-adrenergic receptors. The order of relative potency was: isoproterenol greater than epinephrine greater than norepinephrine. Activation of microvessel adenylate cyclase by prostaglandins E1 and E2 as well as by 2-chloroadenosine was dose related. Twenty-two peptides were tested for possible effects on the microvessel adenylate cyclase. Only vasoactive intestinal polypeptide (VIP) was stimulatory. No inhibitory action was observed. Activation by VIP required guanosine triphosphate and was dose dependent from 10 nM to 1 microM (ED50 = 0.1 microM). At 30 degrees C, stimulation of adenylate cyclase by the peptide increased linearly with time for up to 15 min. The effect of VIP was not inhibited by phentolamine or propranolol, suggesting that its action was not elicited by interaction with alpha- or beta-adrenergic receptors. Activation achieved by VIP and isoproterenol, prostaglandin E1, or 2-chloroadenosine was the sum of the individual stimulations, suggesting that receptors for VIP were distinct from those for isoproterenol, prostaglandin E1, and 2-chloroadenosine.