Characterization of myenteric Delta-opioid receptors (DOR) in porcine ileum

The antidiarrheal effects of opiates are due to their ability to decrease intestinal motility and electrolyte secretion. We have identified DOR mRNA signals in porcine ileum by RT-PCR and localized DOR-like immunoreactivity on myenteric neurons. In this study, we examined the characteristics of DOR in smooth muscle strips from pig ileum. The selective DOR agonists [D-Pen², D-Pen⁵]enkephalin (DPDLE), [D-Ala², D-Leu⁵]enkephalin (DADLE), [D-Ser², Leu⁵, Thr⁶]enkephalin (DSLET) and [D-Ala²]-deltorphin II (D-II) inhibited atropine-sensitive isometric contractions of muscle strips oriented in the circular plane that were elicited by electrical field stimulation (EFS; 10 Hz, 70 V, 100 sec duration). The agonists exhibited a rank order of potency of D-II (IC₅₀ = 1.7 nM) ≥ DSLET > DADLE > DPDPE and relative efficacy of DSLET > D-II > DADLE = DPDPE. EFS-induced contractions were unaffected by the mu-opioid agonist [D-Ala², N-methyl-Phe⁴, Gly⁵-ol]-enkephalin. The selective DOR blockers naltrindole (300 nM) and naltrindole isothiocyanate (3 nM) antagonized D-II actions. For purposes of comparison, we are now examining DOR on submucosal neurons which reduce EFS-induced Cl^- secretion in ileal mucosa. DOR in porcine myenteric neurons may represent the putative DOR-2 subtype; this receptor may mediate the antipropulsive actions of opioids.