Characterization of opioid receptors modulating neurogenic contractions ofcircular muscle from porcine ileum and evidence that delta- and kappa-opioid receptors are coexpressed in myenteric neurons

Opioid receptors (ORs) in the myenteric plexus mediate the antimotility act ions of opioids in the small intestine. In this study, ORs modulating neuro genic circular muscle contractions in the porcine ileum were characterized by pharmacological and immunohistochemical approaches. Circular musclemyent eric plexus strips manifested tetrodotoxin- and atropine-sensitive contract ions during (ON) and after (OFF) electrical field stimulation. The kappa -O R agonists U-50,488H and U-69,593 inhibited ON contractions (pIC(50) = 7.61 and 8.22, respectively). U-69,593 action was inhibited by the kappa -OR an tagonist norbinaltorphimine with an antagonist equilibrium constant (K-e)of 4.2 nM. Selective delta -OR agonists [D-Ala(2)]-deltorphin II, DSLET, DADL E, SNC80, and DPDPE inhibited OFF contractions (pIC(50) = 9.17, 8.63, 8.50, 8.26, and 7.47, respectively). The selective delta -OR antagonist naltribe n reduced the inhibitory actions of SNC80 and DSLET with respective K-e val ues of 2.3 and 3.0 nM. In addition, norbinaltorphimine inhibited the action s of these agonists with respective K-e values of 0.7 and 4.2 nM. The mu -O R agonists DAMGO, loperamide, or morphine exhibited relatively low activiti es in inhibiting ON and OFF contractions. Using primary antisera directed t oward cloned opioid receptors, delta -OR immunoreactivity was observed to b e localized alone or in combination with kappa -OR immunoreactivity in myen teric neurons; mu -OR immunoreactivity was absent. The results suggest that myenteric delta- and kappa -opioid receptors mediate the antitransit effec ts of opioids in the porcine small intestine. These receptors may be functi onally coupled in a subpopulation of myenteric neurons.