The effects of pertussis toxin on vasoconstrictor and vasodilator agents in the pithed rat may not be an indicator of G-protein receptor coupling.
1. In the present study, rats were treated with pertussis toxin (8.4 micrograms, i.v.) to determine whether pertussis toxin-sensitive G-proteins were linked to receptors that mediate effects in the cardiovascular system. 2. In the pithed rat the pressor responses to the alpha-adrenoceptor agonists noradrenaline and (to a lesser extent) methoxamine were attenuated by pertussis toxin treatment; the tachycardia produced by noradrenaline was unaffected. The pressor response to serotonin was also attenuated by pertussis toxin treatment. These observations are consistent with known effects of pertussis toxin on these receptors. 3. The vasodepressor responses to the muscarinic receptor agonist carbachol and to adenosine were reduced by pertussis toxin, suggesting that these events may have been mediated by pertussis toxin-sensitive G-proteins. However, the depressor responses to the beta 2-adrenoceptor agonist salbutamol and to the receptor-independent vasodilator drugs sodium nitroprusside and hydralazine were also reduced by pertussis toxin. These latter effects suggest that caution must be used in interpreting the effects of pertussis toxin since the mechanism of action of these drugs as elucidated in vitro is thought not to involve pertussis toxin-sensitive G-proteins.
Department of Pharmacology, University of Melbourne, Victoria, Australia.
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D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003655:Decerebrate State / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D037342:Pertussis Toxin; D051381:Rats; D017207:Rats, Sprague-Dawley; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects; D011943:Receptors, Adrenergic, beta / Q000187:drug effects; D011976:Receptors, Muscarinic / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000494:pharmacology*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology*
D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D011976:Receptors, Muscarinic; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D010566:Virulence Factors, Bordetella; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins