INHIBITION OF NEURONAL FIRING BY OPIATES - EVIDENCE AGAINST THE INVOLVEMENT OF CYCLIC-NUCLEOTIDES

Extracellular recordings were made in vitro from single neurones of the myenteric plexus of the guinea‐pig ileum. Neuronal firing was inhibited by morphine and normorphine (10 nM to 1 μm). Cyclic adenosine 3′,5′‐monophosphate (cyclic AMP) (100 μm to 1 mm) also inhibited the firing of the majority of the neurones. Prostaglandin E2 usually caused a short‐lasting excitation of myenteric neurones and the phosphodiesterase inhibitor 3‐isobutyl‐l‐methylxanthine was usually without effect on firing rate. The inhibition of neuronal firing by normorphine was unaffected by prior and/or concurrent administration of cyclic AMP, dibutyryl cyclic adenosine 3′,5′‐monophosphate, prostaglandin E2 or 3‐isobutyl‐l‐methylxanthine. As these four treatments might be expected to elevate intracellular levels of cyclic AMP, the results lend no support to the notion that a reduction in intracellular cyclic AMP is essential to the inhibition of firing produced by morphine. 1979 British Pharmacological Society