Mu, but not kappa, opioid agonists induce contractions of the canine small intestine ex vivo.
The proposed kappa opioid receptor agonists ethylketocyclazocine (EK), nalorphine, bremazocine and U-50,488H were evaluated for their ability to produce contractions of isolated, vascularly perfused canine small intestinal segments. Responses to these agonists were compared to those of morphine and phenazocine, a mu benzomorphan. Morphine (0.04-25 micrograms) and phenazocine (0.01-3.0 micrograms) both produced naloxone-reversible contractions, suggesting that the responses were mediated largely by mu opioid receptors. In contrast, the proposed kappa agonists were ineffective in producing intestinal stimulation, with only EK (1-100 micrograms) showing minimal but significant activity at very high doses. We suggest that the effects of EK may be mediated through mu opioid receptors and that kappa receptors appear not to be involved in the contractile response of the dog small intestine to opioids.
Hirning
L D
LD
Porreca
F
F
Burks
T F
TF
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D001575:Benzomorphans / Q000494:pharmacology; D003496:Cyclazocine / Q000031:analogs & derivatives / Q000494:pharmacology; D004246:Dimethylphenylpiperazinium Iodide / Q000494:pharmacology; D004285:Dogs; D016314:Ethylketocyclazocine; D005769:Gastrointestinal Motility / Q000187:drug effects*; D066298:In Vitro Techniques; D007421:Intestine, Small / Q000187:drug effects*; D009020:Morphine / Q000494:pharmacology; D009269:Nalorphine / Q000494:pharmacology; D010620:Phenazocine / Q000494:pharmacology; D011759:Pyrrolidines / Q000494:pharmacology; D011957:Receptors, Opioid / Q000502:physiology*; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu
D000700:Analgesics; D001575:Benzomorphans; D011759:Pyrrolidines; D011957:Receptors, Opioid; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D004246:Dimethylphenylpiperazinium Iodide; D016314:Ethylketocyclazocine; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D009020:Morphine; C027248:bremazocine; D010620:Phenazocine; D003496:Cyclazocine; D009269:Nalorphine