Regulatory role of enteric mu and kappa opioid receptors in the release of acetylcholine and norepinephrine from guinea pig ileum.
We examined the role of opioid receptor subtypes in the contraction and release of acetylcholine (ACh) and norepinephrine in longitudinal muscle-myenteric plexus preparations of the guinea pig ileum. [D-Ala2, N-Me-Phe4, Gly5-ol]enkephalin (DAMGO) (10(-8) to 10(-5) M) inhibited the contraction and the release of ACh evoked by 0.2 and 1 Hz of electrical stimulation (ES), whereas the response to 5 Hz was enhanced by low concentrations of DAMGO (10(-9) to 10(-8) M) and inhibited by high concentrations (10(-7) to 10(-5) M); naloxone antagonized these effects. In preparations treated with yohimbine, DAMGO inhibited the ES (5 Hz)-evoked contraction and ACh release, but failed to enhance either effect. Dynorphin-A inhibited the contraction and ACh release evoked by 0.2, 1 and 5 Hz of ES, and the effect of dynorphin-A was mimicked by U-69593 [5 alpha,7 alpha,8 beta-(-)-N-methyl-N-[7- (pyrrolinyl)-1-ozaspiro(4,5)dec-8-yl]-benzene] and antagonized by MR 2266 [(-)-alpha-5,9-diethyl-2-(3-furylmethyl)-2'-hydroxy-6,7-benzomorphan]. The release of norepinephrine evoked by 5 Hz of ES was inhibited by DAMGO (10(-10) to 10(-6) M), but not by U-69593, and the effect of DAMGO was antagonized by naloxone. Thus, it would appear that mu-opioid receptors are present on both cholinergic and adrenergic neurons, whereas kappa-opioid receptors are present on cholinergic neurons. The affinity of DAMGO was 30 times higher for the mu-opioid receptors on the adrenergic than on the cholinergic neurons.(ABSTRACT TRUNCATED AT 250 WORDS)
Nakayama
S
S
Department of Pharmacology, Kobe University School of Medicine, Japan.
Taniyama
K
K
Matsuyama
S
S
Ohgushi
N
N
Tsunekawa
K
K
Tanaka
C
C
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004399:Dynorphins / Q000494:pharmacology; D004558:Electric Stimulation; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D004745:Enkephalins / Q000494:pharmacology; D005260:Female; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism*; D011957:Receptors, Opioid / Q000187:drug effects / Q000502:physiology*; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu
D004745:Enkephalins; D011957:Receptors, Opioid; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D004399:Dynorphins; D000109:Acetylcholine; D009638:Norepinephrine