Effect of pertussis toxin treatment on postjunctional alpha-1 and alpha-2 adrenoceptor function in the cardiovascular system of the pithed rat.
The role of pertussis toxin sensitive guanine nucleotide regulatory proteins (G-proteins) in the signal transduction processes involved in postjunctional vascular alpha-1 and alpha-2 adrenoceptor-mediated vasoconstriction has been investigated in the cardiovascular system of the pithed rat. Pertussis toxin pretreatment (50 micrograms/kg i.v., 3 days before experimentation) produced a marked inhibition of the alpha-2 adrenoceptor-mediated pressor response to B-HT 933. In contrast, pertussis toxin treatment had only a small effect on the alpha-1 adrenoceptor-mediated pressor response to cirazoline. However, after elimination of the alpha-1 adrenoceptor reserve for cirazoline with phenoxybenzamine (0.1 mg/kg i.v.), the pressor response to this agonist became highly sensitive to inhibition by pertussis toxin treatment. This pattern of inhibition of alpha-1 and alpha-2 adrenoceptor-mediated pressor responses by pertussis toxin is identical to that produced by inhibition of extracellular calcium influx by a high dose of the calcium channel antagonist, nifedipine (1.5 mg/kg i.a.), suggesting that those components of the alpha-1 and alpha-2 adrenoceptor-mediated vasoconstrictor processes that are dependent upon the translocation of extracellular calcium may involve a pertussis toxin sensitive G-protein.(ABSTRACT TRUNCATED AT 250 WORDS)
Nichols
A J
AJ
Department of Pharmacology, Smith Kline and French Laboratories, King of Prussia, Pennsylvania.
Motley
E D
ED
Ruffolo
R R
RR
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001381:Azepines / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects*; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000187:drug effects; D000242:Cyclic AMP / Q000096:biosynthesis; D003655:Decerebrate State; D019204:GTP-Binding Proteins / Q000502:physiology; D007093:Imidazoles / Q000494:pharmacology; D008297:Male; D037342:Pertussis Toxin; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology*
D001381:Azepines; D015220:Calcium Channels; D007093:Imidazoles; D011942:Receptors, Adrenergic, alpha; D010566:Virulence Factors, Bordetella; D000804:Angiotensin II; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; C015603:azepexole; D000242:Cyclic AMP; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; C014282:cirazoline; D002118:Calcium