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

Single-fiber recordings were made from the decentralized right cervical vag us nerve (hyponodosal) of the rat. A total of 56 afferent fibers that respo nded to gastric distension (GD) were studied: 6 fibers were stimulated by p hasic balloon GD, 50 by fluid GD. All fibers gave increasing responses to i ncreasing pressures of GD (5-60 mmHg). The effects of mu-opioid (morphine), delta-opioid (SNC80), and kappa-opioid (EMD61,753, U62,066) receptor agoni sts were rested on responses of afferent fibers to GD. Morphine, administer ed systemically over a broad dose range (10 mu g to 31 mg/kg, cumulative), had no effect on either resting activity or responses of vagal afferent fib ers to CD. Similarly, the delta-opioid receptor agonist SNC80 (0.05-3.2 mg/ kg) did not affect resting activity or responses to GD. In contrast, cumula tive 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 m oderately attenuated by a nonselective dose (4 mg/kg) of naloxone hydrochlo ride; the kappa-opioid receptor-selective antagonist nor-BNI (20 mg/kg) was ineffective. These results demonstrate that kappa-, but not mu- or delta-o pioid receptor agonists modulate visceral sensation conveyed by vagal affer ent fibers innervating the stomach. Given that kappa-opioid receptor agonis ts effects were only modestly antagonized by naloxone and not at all by nor -BNI, the results point to a novel site of action.