Interaction of vascular alpha-1 adrenoceptors with multiple signal transduction pathways.
In the rat vasculature, a single alpha 1-adrenoceptor may be coupled to two distinct G proteins, one of which regulates phospholipase C activity and is insensitive to pertussis toxin, and another which regulates calcium channel function and is highly sensitive to inhibition by pertussis toxin. alpha 1-Adrenoceptor agonists may in theory activate both pathways, but the efficiency of alpha 1-adrenoceptor coupling to the pertussis-toxin-insensitive pathway is low relative to the other pathway that couples the alpha 1-adrenoceptor to calcium channels. As such, only full agonists with high intrinsic efficacy can activate both pathways, whereas partial agonists, by virtue of their lower intrinsic efficacies, are less able to activate the pertussis-toxin-insensitive pathway, thereby rendering partial alpha 1-adrenoceptor agonists more sensitive than full alpha 1-adrenoceptor agonists to inhibition by calcium channel blockers and pertussis toxin.
Ruffolo
R R
RR
Department of Pharmacology, SmithKline Beecham Pharmaceuticals, King of Prussia, Pa.
Nichols
A J
AJ
Oriowo
M A
MA
D000818:Animals; D001808:Blood Vessels / Q000502:physiology*; D002118:Calcium / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000502:physiology; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*
D011942:Receptors, Adrenergic, alpha; D019204:GTP-Binding Proteins; D002118:Calcium