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 processes that link occupation of mu receptors to the opening of potassium channels on myenteric neurons.
Department of Physiology, Flinders University of South Australia, Bedford Park.
S M
SM
Johnson
N P
NP
Pillai
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000494:pharmacology*; D004723:Endorphins / Q000494:pharmacology*; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D004745:Enkephalins / Q000494:pharmacology; D005260:Female; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D009197:Myenteric Plexus / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D009474:Neurons / Q000187:drug effects* / Q000502:physiology
D004723:Endorphins; D004745:Enkephalins; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D005576:Colforsin; D003994:Bucladesine; D000242:Cyclic AMP; D015056:1-Methyl-3-isobutylxanthine