Central effect of mu-opioid agonists on antral motility in conscious rats

Abstract

Centrally applied opioids delay gastric emptying and inhibit intestinal transit. However, the mechanism of inhibitory effects of central opioids on gastric motility still remains unclear. It also remains unclear which opioid receptor (mu, delta, and kappa) stimulation affects gastric motility. We studied the central effect of opioids on antral motility in conscious rats. A strain gauge transducer was implanted on the gastric antrum to record the circular muscle contractions. The area under the curve of the antral motility, calculated as a motility index, was evaluated before and after the intracerebroventricular (icv) injection of various opioid agonists in each rat. [D-Ala2, N-Me-Phe4, Gly5-ol] enkephalin (DAMGO, 0.1-10 nmol), a mu-opioid selective agonist, significantly inhibited antral motility in a dose-dependent manner (n=4). The motility index was significantly decreased to 47.3+/-10.8% (n=4) of controls at 20 min after icv injection of DAMGO (1.0 nmol). In contrast, [D-pen2, L-Pen5] enkephalin (DADLE, 1.0 nmol), a delta-opioid selective agonist, and U50,488 (1.0 nmol), a kappa-opioid selective agonist, had no significant effects on antral motility. Pretreatment with subcutaneous guanethidine (5 mg/kg) and propranolol (1 mg/kg), but not phentolamine (1 mg/kg), significantly antagonized the inhibitory effect of DAMGO (1.0 nmol). Reduced motility index induced by DAMGO (1.0 nmol) was restored from 48.7+/-3.5% to 88.6+/-10.9% (n=5) and 80.4+/-2.2% (n=5) by guanethidine and propranolol, respectively. Our findings suggest that central mu-opioid receptor has major inhibitory effects on antral motility in conscious rats. The inhibitory effects of mu-opioid receptors are mediated via sympathetic pathways and beta-adrenoceptors.