Pharmacologic differentiation between pre- and postjunctional alpha 2-adrenoceptors by SK&F 104078.
Most alpha 2-adrenoceptor antagonists do not discriminate between pre- and postjunctional alpha 2-adrenoceptors, and this has led to the commonly held belief that pre- and postjunctional alpha 2-adrenoceptors may represent one homogeneous population of receptors. SK&F 104078 has been shown to be a potent antagonist at postjunctional alpha 2-adrenoceptors at concentrations that do not block prejunctional alpha 2-adrenoceptors. Thus, SK&F 104078 is a competitive postjunctional alpha 2-adrenoceptor antagonist in canine and rabbit saphenous veins, canine saphenous artery and human platelet with a dissociation constant of approximately 100 nmol/l. Conversely, SK&F 104078 is inactive as a prejunctional alpha 2-adrenoceptor antagonist in atria from dog, guinea pig, rabbit and rat, and in guinea-pig ileum at concentrations up to 10,000 nmol/l. Likewise, SK&F 104078 has the ability to block postjunctional arterial alpha 2-adrenoceptors in vivo in the pithed rat at doses that do not inhibit prejunctional alpha 2-adrenoceptors in the same model. The results suggest that pre- and postjunctional alpha 2-adrenoceptors may not represent one homogeneous class, but rather are discrete subtypes of the alpha 2-adrenoceptor that may be differentiated by SK&F 104078.
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D001552:Benzazepines; D003655:Decerebrate State; D004285:Dogs; D004558:Electric Stimulation; D006168:Guinea Pigs; D066298:In Vitro Techniques; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology; D009469:Neuromuscular Junction / Q000187:drug effects; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects*; D009435:Synaptic Transmission / Q000187:drug effects
D000317:Adrenergic alpha-Antagonists; D001552:Benzazepines; D011942:Receptors, Adrenergic, alpha; C054935:SK&F 104078