Inhibition of neuronally induced relaxation of canine lower esophageal sphincter by opioid peptides.
Opioid peptides have profound effects on gut motility. To assess their actions on enteric neurons regulating sphincteric smooth muscle, the ability of several opioid agonists to antagonize the neuronally induced relaxation of canine lower esophageal sphincter smooth muscle was examined. Opioid peptides selective for mu (FK 33-824) or delta [( D-Pen2,D-Pen5]enkephalin) receptors produced a concentration dependent inhibition of electrical field stimulation (EFS)-induced relaxation. In contrast, neither kappa (ketocycloclazine) or sigma (SK & F 10047) opioid agonists were potent inhibitors of EFS-induced relaxation. This inhibition was relatively selective for opioid agonists since BHT 933 (alpha 2 adrenoceptor agonist) and SK & F 89124 (D2 dopamine agonist) did not inhibit EFS-induced relaxation. Furthermore, naloxone antagonized the effects of both FK 33-824 and DPDPE. These functional data suggest that opioid receptors are present on sphincteric intrinsic inhibitory neurons and that stimulation of these neuronal receptors can regulate lower esophageal sphincter relaxation.
Department of Pharmacology, Smith Kline Beecham Pharmaceuticals, King of Prussia, PA 19406-0939.
M S
MS
Barnette
M
M
Grous
C D
CD
Manning
J F
JF
Callahan
F C
FC
Barone
D000818:Animals; D001341:Autonomic Nervous System / Q000502:physiology; D003496:Cyclazocine / Q000031:analogs & derivatives / Q000494:pharmacology; D005405:D-Ala(2),MePhe(4),Met(0)-ol-enkephalin / Q000494:pharmacology; D004285:Dogs; D004558:Electric Stimulation; D004723:Endorphins / Q000494:pharmacology*; D020881:Enkephalin, D-Penicillamine (2,5)-; D004745:Enkephalins / Q000494:pharmacology; D004943:Esophagogastric Junction / Q000187:drug effects / Q000294:innervation / Q000502:physiology; D016314:Ethylketocyclazocine; D066298:In Vitro Techniques; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects* / Q000294:innervation; D009474:Neurons / Q000502:physiology*; D010620:Phenazocine / Q000031:analogs & derivatives / Q000494:pharmacology
D004723:Endorphins; D004745:Enkephalins; D016314:Ethylketocyclazocine; D005405:D-Ala(2),MePhe(4),Met(0)-ol-enkephalin; C012134:SK&F 10047; D020881:Enkephalin, D-Penicillamine (2,5)-; D010620:Phenazocine; D003496:Cyclazocine