Effect of pertussis toxin treatment on postjunctional alpha-1 and alpha-2 adrenoceptor function in the cardiovascular system of the pithed rat

J Pharmacol Exp Ther. 1989 Apr;249(1):203-9.

Abstract

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)

MeSH terms

  • 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / pharmacology
  • Angiotensin II / pharmacology
  • Animals
  • Azepines / pharmacology
  • Blood Pressure / drug effects*
  • Calcium / metabolism
  • Calcium Channels / drug effects
  • Cyclic AMP / biosynthesis
  • Decerebrate State
  • GTP-Binding Proteins / physiology
  • Imidazoles / pharmacology
  • Male
  • Pertussis Toxin*
  • Rats
  • Rats, Inbred Strains
  • Receptors, Adrenergic, alpha / drug effects*
  • Virulence Factors, Bordetella / pharmacology*

Substances

  • Azepines
  • Calcium Channels
  • Imidazoles
  • Receptors, Adrenergic, alpha
  • Virulence Factors, Bordetella
  • Angiotensin II
  • 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester
  • azepexole
  • Cyclic AMP
  • Pertussis Toxin
  • GTP-Binding Proteins
  • cirazoline
  • Calcium