Abstract
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.
MeSH terms
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Adrenergic alpha-2 Receptor Antagonists
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Adrenergic alpha-Agonists / metabolism
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Adrenergic alpha-Agonists / pharmacology
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Adrenergic alpha-Antagonists / pharmacology*
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Analgesics / pharmacology
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Animals
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Colon / innervation
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Dose-Response Relationship, Drug
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Electric Stimulation
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Enkephalin, Ala(2)-MePhe(4)-Gly(5)-
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Enkephalins / pharmacology
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Guinea Pigs
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Myenteric Plexus / chemistry*
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Myenteric Plexus / drug effects
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Myenteric Plexus / metabolism
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Naloxone / pharmacology
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Naltrexone / analogs & derivatives
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Naltrexone / pharmacology
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Narcotic Antagonists / pharmacology
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Neurotransmitter Agents / metabolism
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Norepinephrine / metabolism
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Norepinephrine / pharmacology
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Pyrrolidines / pharmacology
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Receptors, Adrenergic, alpha-2 / metabolism*
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Receptors, Opioid, kappa / agonists
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Receptors, Opioid, kappa / antagonists & inhibitors
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Receptors, Opioid, kappa / metabolism*
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Receptors, Opioid, mu / agonists
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Receptors, Opioid, mu / antagonists & inhibitors
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Receptors, Opioid, mu / metabolism*
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Yohimbine / pharmacology
Substances
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Adrenergic alpha-2 Receptor Antagonists
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Adrenergic alpha-Agonists
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Adrenergic alpha-Antagonists
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Analgesics
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Enkephalins
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Narcotic Antagonists
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Neurotransmitter Agents
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Pyrrolidines
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Receptors, Adrenergic, alpha-2
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Receptors, Opioid, kappa
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Receptors, Opioid, mu
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Enkephalin, Ala(2)-MePhe(4)-Gly(5)-
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ICI 204448
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Yohimbine
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Naloxone
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norbinaltorphimine
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Naltrexone
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Norepinephrine