Differential effects of mu-, delta-, and kappa-opioid receptor agonists on mechanosensitive gastric vagal afferent fibers in the rat.

Abstract

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.