Effects of pertussis toxin on opioid regulation of catecholamine release from rat and guinea pig brain slices.
Opioid agonists selective for mu-, delta-, and kappa-receptors are all capable of regulating the stimulated release of noradrenaline from three terminal fields (cortex, hippocampus, and cerebellum) of the noradrenergic projections from locus coeruleus in the guinea pig brain. Intracerebroventricular injections of pertussis toxin abolished the ability of a mu-selective agonist and of a delta-selective agonist to inhibit stimulated noradrenaline release, but left unaffected the concentration-related inhibition of NE release by a kappa agonist. Thus, mu- and delta-receptors have been shown to be coupled to their effector system in these noradrenergic neurons via guanyl nucleotide binding proteins (G proteins) which are sensitive to pertussis toxin, while kappa-receptors in the same neurons appear to be coupled through a different mechanism which is significantly less sensitive to pertussis toxin. In contrast to opioid receptor regulation of noradrenaline release in guinea pig hippocampus, mu-, but not delta- or kappa-agonists are capable of regulation of stimulated noradrenaline release from rat hippocampus and cortex, and kappa-, but not mu- or delta-agonists are capable of inhibiting the stimulated release of dopamine from rat striatum and cortex. Pertussis toxin injections significantly attenuated mu-agonist inhibition of noradrenaline release, but had no effect on the ability of a kappa-selective agonist to regulated dopamine release, confirming the insensitivity of the kappa-receptor-effector coupling system to pertussis toxin.
Werling
L L
LL
Department of Pharmacology, Uniformed Services University, Bethesda, Maryland 20814-4799.
McMahon
P N
PN
Cox
B M
BM
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects*; D002395:Catecholamines / Q000378:metabolism*; D003342:Corpus Striatum / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D020881:Enkephalin, D-Penicillamine (2,5)-; D004745:Enkephalins / Q000494:pharmacology; D006168:Guinea Pigs; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D007276:Injections, Intraventricular; D008297:Male; D009294:Narcotics / Q000494:pharmacology*; D037342:Pertussis Toxin; D011759:Pyrrolidines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid / Q000502:physiology; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D010566:Virulence Factors, Bordetella / Q000008:administration & dosage / Q000494:pharmacology*
D002395:Catecholamines; D004745:Enkephalins; D009294:Narcotics; D011759:Pyrrolidines; D011957:Receptors, Opioid; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D010566:Virulence Factors, Bordetella; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D020881:Enkephalin, D-Penicillamine (2,5)-; D037342:Pertussis Toxin; D004298:Dopamine