Differential effects of mu-, delta-, and kappa-opioid receptor agonists on mechanosensitive gastric vagal afferent fibers in the rat.
Single-fiber recordings were made from the decentralized right cervical vagus nerve (hyponodosal) of the rat. A total of 56 afferent fibers that responded to gastric distension (GD) were studied: 6 fibers were stimulated by phasic balloon GD, 50 by fluid GD. All fibers gave increasing responses to increasing pressures of GD (5-60 mmHg). The effects of mu-opioid (morphine), delta-opioid (SNC80), and kappa-opioid (EMD61,753, U62,066) receptor agonists were tested on responses of afferent fibers to GD. Morphine, administered systemically over a broad dose range (10 microg to 31 mg/kg, cumulative), had no effect on either resting activity or responses of vagal afferent fibers to GD. Similarly, the delta-opioid receptor agonist SNC80 (0.05-3.2 mg/kg) did not affect resting activity or responses to GD. In contrast, cumulative intra-arterial doses of the kappa-opioid receptor agonist EMD61,753 or U62,066 dose dependently attenuated afferent fiber responses to GD. Doses producing inhibition to 50% of the control response to GD of EMD61,753 (8.0 mg/kg) and U62,066 (8.8 mg/kg) did not differ. The effect of U62,066 was moderately attenuated by a nonselective dose (4 mg/kg) of naloxone hydrochloride; the kappa-opioid receptor-selective antagonist nor-BNI (20 mg/kg) was ineffective. These results demonstrate that kappa-, but not mu- or delta-opioid receptor agonists modulate visceral sensation conveyed by vagal afferent fibers innervating the stomach. Given that kappa-opioid receptor agonists effects were only modestly antagonized by naloxone and not at all by nor-BNI, the results point to a novel site of action.
Ozaki
N
N
Department of Pharmacology, College of Medicine, University of Iowa, Iowa City, Iowa 52242, USA.
Sengupta
J N
JN
Gebhart
G F
GF
D000081:Acetamides / Q000494:pharmacology; D000700:Analgesics / Q000494:pharmacology; D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D002404:Catheterization; D004558:Electric Stimulation; D008297:Male; D008465:Mechanoreceptors / Q000502:physiology; D009020:Morphine / Q000494:pharmacology; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009412:Nerve Fibers / Q000737:chemistry / Q000187:drug effects / Q000502:physiology; D009475:Neurons, Afferent / Q000737:chemistry / Q000187:drug effects* / Q000648:ultrastructure; D010146:Pain / Q000188:drug therapy / Q000503:physiopathology; D010879:Piperazines / Q000494:pharmacology; D011759:Pyrrolidines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011957:Receptors, Opioid / Q000819:agonists*; D017465:Receptors, Opioid, delta / Q000819:agonists; D017473:Receptors, Opioid, kappa / Q000819:agonists; D017450:Receptors, Opioid, mu / Q000819:agonists; D013270:Stomach / Q000294:innervation*; D014630:Vagus Nerve / Q000737:chemistry / Q000166:cytology* / Q000502:physiology*
D000081:Acetamides; D000700:Analgesics; D000701:Analgesics, Opioid; D001549:Benzamides; D009292:Narcotic Antagonists; D010879:Piperazines; D011759:Pyrrolidines; D011957:Receptors, Opioid; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; C088464:4-(alpha-(4-allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl)-N,N-diethylbenzamide; D009270:Naloxone; D009020:Morphine; C092095:asimadoline; C051272:spiradoline