Opioid inhibition of cholinergic transmission in the guinea-pig ileum is independent of intracellular cyclic AMP.
This study examined whether the inhibitory actions of opioids in the guinea-pig ileum were influenced by agents which mimic or elevate intracellular cyclic adenosine 3',5'-monophosphate (cyclic AMP) levels. In longitudinal muscle-myenteric plexus preparations, the mu agonist, [D-Ala2,NMePhe4,Gly-ol5]enkephalin (DAGO) and the kappa agonist, dynorphin A-(1-13) depressed contractions of the longitudinal muscle evoked by electrical stimulation of myenteric neurons. Mean IC50 values were 19 and 2.8 nM for DAGO and dynorphin, respectively. Neither forskolin, cholera toxin nor dibutyryl cyclic AMP affected significantly the IC50s for the opioid agonists. The experiments suggest that mu and kappa agonists inhibit excitatory cholinergic transmission to the longitudinal muscle by intracellular effector mechanisms that do not involve cyclic AMP.
Department of Physiology, Flinders University of South Australia, Bedford Park.
S M
SM
Johnson
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D002772:Cholera Toxin / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000502:physiology*; D004399:Dynorphins / Q000494:pharmacology; D004558:Electric Stimulation; D005260:Female; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects / Q000294:innervation / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D009294:Narcotics / Q000494:pharmacology*; D010275:Parasympathetic Nervous System / Q000187:drug effects* / Q000378:metabolism; D011957:Receptors, Opioid / Q000378:metabolism; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D009435:Synaptic Transmission / Q000187:drug effects*
D009294:Narcotics; D011957:Receptors, Opioid; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D005576:Colforsin; D003994:Bucladesine; D004399:Dynorphins; D002217:Carbachol; D002772:Cholera Toxin; D000242:Cyclic AMP; D015056:1-Methyl-3-isobutylxanthine