enkephalin--leucine-2-alanine and difenoxin

The potency order of opiate agonists at decreasing the rate of peristalsis in the rat isolated ileum was: difenoxin > loperamide > DADLE (D-Ala2-D-Leu5-enkephalin) > morphine > DSLET (D-Ser2,Leu5-Thr6-enkephalin). U-50488 (trans 3,4-dichloro-N-methyl-N-(2-(1-pyrrolidinyl) cyclohexyl) benzeneacetamide methane sulphonate) was inactive at 300 nM. Naloxone (400 nM) caused a significant 1.52-fold increase in the rate of peristaltic contractions and inhibited the effects of the active opiate agonists. The apparent pA2 values of naloxone were similar using difenoxin, loperamide and morphine as agonists, but the value was slightly, though significantly lower when DADLE was the agonist. It is suggested that the previously identified delta-opiate receptors of the rat small intestine have a functional role in suppressing the peristaltic reflex. The same response is subserved by mu-opiate receptors and either of these opiate-receptor subtypes could be activated by endogenous enkephalins.

Topics: 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; Analgesics; Animals; Antidiarrheals; Diphenoxylate; Enkephalin, Leucine; Enkephalin, Leucine-2-Alanine; Ileum; Linear Models; Loperamide; Morphine; Peristalsis; Pyrrolidines; Rats; Receptors, Opioid, delta; Receptors, Opioid, mu