Pertussis toxin differentiates between alpha 1- and alpha 2-adrenoceptor-mediated inhibition of noradrenaline release from rat kidney cortex.
In slices of rat kidney cortex incubated in [3H]noradrenaline, the alpha 1-adrenoceptor agonist methoxamine (10 microM), the alpha 2-adrenoceptor agonist clonidine (0.1 microM), as well as adenosine (10 microM), inhibited the electrical stimulation-induced (S-I) outflow of radioactivity, at a stimulation frequency of 1 Hz. Prior treatment of rats with pertussis toxin (25 micrograms/kg i.v.), which abolished the negative inotropic effect of carbachol (10 microM) on isolated atria, prevented the inhibition caused by methoxamine, but not that caused by clonidine or adenosine. At a stimulation frequency of 5 Hz, the alpha 2-adrenoceptor antagonist idazoxan (0.1 microM) and the prostaglandin synthesis inhibitor indomethacin (10 microM) both facilitated the S-I outflow of radioactivity, and neither of these effects were altered by pertussis toxin. These results suggest that a pertussis toxin sensitive G-protein is involved in alpha 1-adrenoceptor inhibition of noradrenaline release, but not in alpha 2-adrenoceptor, adenosine or prostaglandin inhibition.
Murphy
T V
TV
Department of Pharmacology, University of Melbourne, Parkville, Victoria, Australia.
Majewski
H
H
D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D003000:Clonidine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D004558:Electric Stimulation; D006321:Heart / Q000187:drug effects; D007672:Kidney Cortex / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008729:Methoxamine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D009200:Myocardial Contraction / Q000187:drug effects; D009638:Norepinephrine / Q000378:metabolism*; D037342:Pertussis Toxin; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology*
D011942:Receptors, Adrenergic, alpha; D010566:Virulence Factors, Bordetella; D002217:Carbachol; D037342:Pertussis Toxin; D008729:Methoxamine; D003000:Clonidine; D009638:Norepinephrine