The role of pertussis-toxin-sensitive guanine nucleotide regulatory proteins (G proteins) in the signal transduction processes involved in post-junctional vascular α1-adrenoceptor-mediated vasoconstnction has been investigated in the pithed rat using two chemical classes of α-adrenoceptor agonists, the phenethylamines and imidazolines, in order to determine if they utilize different signal transduction mechanisms. Pertussis toxin pre-treatment (50 µg/kg, i.v., 3 days prior to experimentation) slightly inhibited the pressor response to the full α1-adrenoceptor agonist of the phen class (–)-norepinephrine (in the presence of rauwolscine, 1 mg/kg, i.v.), whereas it markedly inhibited the pressor response to the partial α1-adrenoceptor agonist of the imidazoline class oxymetazoline (in the presence of rauwolscine, 1 mg/kg, i.v.). However, after elimination of the α1-adrenoceptor reserve for (–)-norepinephrine with phenoxybenzamine (0.1 mg/kg, i.v.), the pressor response to this agonist became sensitive to inhibition by pertussis toxin treatment. The pattern of inhibition of α1- adrenoceptor-mediated pressor responses produced by pertussis toxin was similar to that produced by the calcium channel antagonist nifedipine (1 mg/kg, i.a.). The results support the hypothesis that vascular α1-adreno-ceptors may be coupled to a G protein which is sensitive to pertussis toxin and which couples the α1-adrenoceptor to the influx of extracellular calcium, with possibly another G protein that is insensitive to pertussis toxin that couples the α1-adrenoceptor to the release of intracellular calcium. The intrinsic efficacy of the agonist, and not its chemical class, determines which signal transduction mechanisms will be utilized.

Keywords:
α1-Adrenoceptors, Pithed rats, Pertussis toxin G proteins, Full agonist, Partial agonist, Imidazolines, Phenethylamines
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© 1992 S. Karger AG, Basel
1992
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