PHARMACOLOGICAL CHARACTERIZATION OF PURINOCEPTOR-MEDIATED CONSTRICTION OF SUBMUCOSAL ARTERIOLES IN GUINEA-PIG ILEUM

Sympathetic nerve stimulation causes a constriction of submucosal arte rioles that is mediated by ATP acting at P-2 receptors. In the present study, we examined the P-2 receptor subtype mediating this response, A computer-assisted video monitoring system measured drug-induced chan ges in arteriolar diameter (resting diameter approximately 40-80 mu m) in pieces of submucosa in vitro. The rank-order potency for vasoconst riction caused by several ATP analogs was alpha,beta-methylene ATP (al pha,beta-MeATP) > beta,gamma-methylene ATP = 2-methylthioATP > ATP > A DP. Constrictions caused by alpha,beta-MeATP were competitively antago nized by suramin (Kg = 3.2 mu M) and were noncompetitively blocked by pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid (K-B = 0.5 mu M). Norepinephrine-induced constrictions were not affected by suramin (10 0 mu M) or by pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid (3 mu M). Extracellular solutions with 0 added calcium prevented constric tions caused by alpha,beta-MeATP (0.1-1.0 mu M), but not those caused by norepinephrine (3 and 10 mu M). Nifedipine (0.3 and 1 mu M) reduced constrictions caused by 40 and 60 mM extracellular potassium chloride , but not those caused by alpha,beta MeATP. These data indicate that P -2X receptors mediate constriction of submucosal arterioles. P-2X-medi ated vasoconstriction is dependent on extracellular calcium, but calci um entry through nifedipine-sensitive calcium channels does not contri bute to P-2X-mediated vasoconstriction.