AJP - Gastrointestinal and Liver Physiology, Vol 254, Issue 2 224-G231, Copyright © 1988 by American Physiological Society
Sites of action of mu-, kappa- and sigma-opiate receptor agonists at the feline ileocecal sphincter
A. Ouyang, P. Vos and S. Cohen
Department of Medicine, Hospital of the University of Pennsylvania, Philadelphia 19104.
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.
