Modulation of neurotransmitter release by opioid mu- and kappa-receptors from adrenergic terminals in the myenteric plexus of the guinea-pig colon: effect of alpha 2-autoreceptor blockade.
We have studied the effect of [D-Ala2,N-Me-Phe4,Gly-ol5]-enkephalin (DAMGO, opioid mu-receptor agonist) and ICI-204,448 (kappa-receptor agonist) on endogenous noradrenaline release in the guinea-pig isolated distal colon. DAMGO enhances noradrenaline over-flow and this effect is antagonized by naloxone (pIC50 = 10.27) and nor-binaltorphimine (pIC50 = 7.97), and concentration-dependently turned into inhibition by yohimbine. ICI-204,448 inhibits noradrenaline overflow and is antagonized by naloxone (pIC50 = 9.38) and nor-binaltorphimine (pIC50 = 10.48), but is not affected by yohimbine. Evidence is thus given that mu- and kappa-opioid receptors modulate noradrenaline release in the guinea-pig colon. Modifications by yohimbine of the effect of DAMGO indicate the existence of a functional relationship between mu-receptors and alpha(2)-autoreceptors in this model.
Cosentino
M
M
Department of Internal Medicine and Therapeutics, II Faculty of Medicine, University of Pavia, Varese VA, Italy.
Marino
F
F
Bombelli
R
R
Ferrari
M
M
Rasini
E
E
Giaroni
C
C
Lecchini
S
S
Frigo
G
G
D058669:Adrenergic alpha-2 Receptor Antagonists; D000316:Adrenergic alpha-Agonists / Q000378:metabolism / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D003106:Colon / Q000294:innervation; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D004745:Enkephalins / Q000494:pharmacology; D006168:Guinea Pigs; D009197:Myenteric Plexus / Q000737:chemistry* / Q000187:drug effects / Q000378:metabolism; D009270:Naloxone / Q000494:pharmacology; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D018377:Neurotransmitter Agents / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism / Q000494:pharmacology; D011759:Pyrrolidines / Q000494:pharmacology; D018341:Receptors, Adrenergic, alpha-2 / Q000378:metabolism*; D017473:Receptors, Opioid, kappa / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D017450:Receptors, Opioid, mu / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015016:Yohimbine / Q000494:pharmacology
D058669:Adrenergic alpha-2 Receptor Antagonists; D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D000700:Analgesics; D004745:Enkephalins; D009292:Narcotic Antagonists; D018377:Neurotransmitter Agents; D011759:Pyrrolidines; D018341:Receptors, Adrenergic, alpha-2; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; C060223:ICI 204448; D015016:Yohimbine; D009270:Naloxone; C051844:norbinaltorphimine; D009271:Naltrexone; D009638:Norepinephrine