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.
|Original language||English (US)|
|State||Published - Dec 1 1997|