Sites of action of mu-, kappa- and sigma-opiate receptor agonists at the feline ileocecal sphincter.
The sites of action of several opiate agonists at the feline ileocecal sphincter (ICS) were studied. Dose-response curves for the relatively specific ligands for the mu-, kappa-, and sigma-receptors were determined using morphine (mu-receptors), dynorphin-(1-13) (kappa-receptors), and N-allylnormetazocine (sigma-receptors). Each agonist results in a contractile ICS response. The ICS responded stereospecifically to the levo-isomer of N-allylnormetazocine. Atropine (30 micrograms/kg) or naloxone (100 micrograms/kg) antagonized the ICS response to morphine and to (-)-N-allylnormetazocine. Higher doses of naloxone were required to inhibit the ICS response to dynorphin. Neither atropine nor tetrodotoxin inhibited the ICS response to dynorphin. The ICS response to dynorphin was enhanced after tetrodotoxin. Morphine tachyphylaxis inhibited the ICS response to (-)-N-allylnormetazocine and vice versa. The ICS response to morphine was unaffected by vagotomy but inhibited by trimethaphan camsylate. This study suggests that dynorphin (kappa-receptor) acts at a smooth muscle receptor to mediate contraction and a neural receptor to mediate relaxation, while (-)-N-allylnormetazocine acts at the ICS via a mu-receptor. mu-Receptor activation causes ICS contraction via a cholinergic pathway.
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002415:Cats; D004399:Dynorphins / Q000494:pharmacology; D005730:Ganglionic Blockers / Q000494:pharmacology; D007080:Ileocecal Valve / Q000187:drug effects / Q000502:physiology*; D009020:Morphine / Q000494:pharmacology; D009270:Naloxone / Q000494:pharmacology; D010620:Phenazocine / Q000031:analogs & derivatives / Q000494:pharmacology; D011957:Receptors, Opioid / Q000187:drug effects / Q000502:physiology*; D013618:Tachyphylaxis; D013779:Tetrodotoxin / Q000494:pharmacology; D014628:Vagotomy
D005730:Ganglionic Blockers; D011957:Receptors, Opioid; D009270:Naloxone; D013779:Tetrodotoxin; D004399:Dynorphins; C012134:SK&F 10047; D009020:Morphine; D001285:Atropine; D010620:Phenazocine