Interplay of somatostatin, opioid, and GABA neurons in the regulation of the peristaltic reflex.

The interplay of somatostatin, gamma-aminobutyric acid (GABA), and opioid neurons in the regulation of the descending relaxation phase of peristalsis was examined in isolated rat colonic segments. Release of somatostatin, GABA, vasoactive intestinal peptide (VIP), and L-[3H]citrulline [coproduct and index of nitric oxide (NO) production] increased, and release of Met-enkephalin decreased, during descending relaxation. Somatostatin antiserum (1:50) inhibited GABA and L-[3H]citrulline and reversed Met-enkephalin from decrease below to increase above basal level; exogenous somatostatin had the opposite effect. Bicuculline (GABAA antagonist) inhibited L-[3H]citrulline, had no effect on somatostatin, and reversed Met-enkephalin from decrease below to increase above basal level; exogenous GABA had the opposite effect. Naloxone increased GABA and L-[3H]citrulline but had no effect on somatostatin; exogenous Met-enkephalin had the opposite effect. In all instances the changes in L-[3H]citrulline paralleled those previously obtained with VIP. The results are consistent with the operation of a circuit in which somatostatin neurons inhibit the activity of opioid neurons, causing a decrease in Met-enkephalin. The decrease in Met-enkephalin initiated by somatostatin is accentuated by a reciprocal inhibitory pathway linking GABA and opioid neurons. The decrease in Met-enkephalin eliminates the inhibitory influence of opioid neurons on VIP/NO neurons and leads to increase in VIP, NO, and descending relaxation.