Opioid-controlled adenylate cyclase in the guinea-pig myenteric plexus is confined to nerve somata.

Previous studies with the electrically stimulated longitudinal muscle-myenteric plexus preparation of the guinea-pig ileum suggested that opioid control of adenylate cyclase is confined to nerve somata. No indication was found for an opioid effect on the enzyme at nerve terminals of the neuro-muscular junction. The aim of the present investigation was to directly study the effect of opioids on cAMP generation in nerve fragments associated with somata or terminals of the myenteric plexus. Employing the ultracentrifugation technique an enrichment of cell organelles in fractions relating to either somata or terminals was achieved. Opioid binding studies revealed specific mu-receptors which in both fractions were regulated by GTP. Challenge of these fractions with forskolin and prostaglandin E1, respectively, resulted in an increased production of cAMP regardless of their neuroanatomical assignment. Examining the response of neuronal material to the selective mu-opioid DAMGO ([D-Ala2, MePhe4, Gly-ol5]enkephalin) revealed an inhibitory action on cAMP synthesis in somata-enriched fractions. No effect of DAMGO was observed in material linked to nerve terminals, although the presence of mu-opioid receptors and adenylate cyclase has been demonstrated. We conclude that opioid control of adenylate cyclase in the myenteric plexus of the guinea pig is confined to nerve somata.