Differential Effects of m-, d-, and k-Opioid Receptor Agonists on Mechanosensitive Gastric Vagal Afferent Fibers in the Rat

Ozaki, Noriyuki, J. N. Sengupta, and G. F. Gebhart. Differential effects of m-, d-, and k-opioid receptor agonists on mechanosensitive gastric vagal afferent fibers in the rat. J. Neurophysiol. 83: 2209–2216, 2000. 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 m-opioid (morphine), d-opioid (SNC80), and k-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 mg to 31 mg/kg, cumulative), had no effect on either resting activity or responses of vagal afferent fibers to GD. Similarly, the d-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 k-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 k-opioid receptor-selective antagonist nor-BNI (20 mg/kg) was ineffective. These results demonstrate that k-, but not mor d-opioid receptor agonists modulate visceral sensation conveyed by vagal afferent fibers innervating the stomach. Given that k-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.