Influence of purinoceptors' agonists and antagonists on opossum internal anal sphincter

Abstract

Studies were performed in alpha-chloralose-anesthetized and pancuronium-treated opossums. Resting internal anal sphincter pressures (IASP) were monitored using low-compliant continuously perfused catheters. P1 and P2 purinoceptor agonists, adenosine and ATP, respectively, administered close intra-arterially, caused dose-dependent decreases in the IASP. The inhibitory effect of these agonists on the IASP was tetrodotoxin resistant. Rectal balloon distension (RD) (which mimics the rectoanal inhibitory reflex) caused volume-dependent IAS relaxation. Electrical stimulation of the sacral nerve (SNS) also produced frequency-dependent decreases in IASP. The inhibitory response to adenosine (P1 purinoceptor agonist), ATP (P2 purinoceptor agonist), RD, and SNS on the internal anal sphincter (IAS) was examined before and after 8-phenyltheophylline (P1 purinoceptor antagonist) and alpha,beta-methylene ATP (P2 purinoceptor antagonist that irreversibly binds and desensitizes P2 purinoceptor). P1 and P2 purinoceptor antagonists produced selective antagonism of the inhibitory responses on the IAS of their respective agonists only. Furthermore, high doses of adenosine and ATP produced desensitization and block of their own actions only. The purinoceptors' antagonists, and the desensitization of purinoceptors by high doses of adenosine and ATP, failed to modify the fall in IASP in response to RD or SNS. From these studies we conclude that distinct inhibitory P1 and P2 purinoceptors are present on the IAS smooth muscle. However, these inhibitory purinoceptors may not be responsible for the rectoanal reflex-mediated IAS relaxation.