Hyperpolarization of myenteric neurons by opioids does not involve cyclic adenosine-3′,5′-monophosphate

To investigate the role of cyclic adenosine-3′,5′-monophosphate on the inhibitory actions of opioids in guinea-pig ileum, we made intracellular recordings from the two electrophysiologically defined classes of neurons (S and AH) in the myenteric plexus. The selective opioid mu agonist (d-Ala2,N-Me-Phe4,Gly5-ol)-enkephalin caused a membrane hyperpolarization in 34 out of 67 S neurons but did not affect the membrane potential of AH neurons. The mean amplitude (±S.E.M.) of the hyperpolarization was 8.2 ± 0.8 mV. Forskolin, which activates adenylate cyclase and increases intracellular cyclic adenosine-3′,5′-monophosphate levels, caused a membrane depolarization in AH neurons (9.4 ± 1.9 mV) but did not alter the resting membrane potential of S neurons. Similarly, neither the phosphodiesterase inhibitor, isobutylmethylxanthine, nor the membrane permeable analogue of cyclic adenosine-3′,5′-monophosphate, dibutyryl cyclic adenosine-3′,5′-monophosphate, altered the resting membrane properties of S neurons. Furthermore, none of these agents affected significantly the amplitude of the hyperpolarization of S neurons by (d-Ala2,N-Me-Phe4,Gly5-ol)-enkephalin. The experiments indicate that changes in intracellular cyclic adenosine-3′,5′-monophosphate are not important in the process that link occupation of mu receptors to the opening of potassium channels on myenteric neurons.