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.
Johnson
S M
SM
Department of Physiology, Flinders University of South Australia, Bedford Park.
Pillai
N P
NP
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