Norepinephrine-induced contractions of the rat aorta in the absence of extracellular calcium--I. Effects of alpha-adrenoreceptor blockers.
The rat aorta responds biphasically to norepinephrine (NE) in calcium-free medium. The two components of the contraction (phasic followed by tonic) are dissociable, both are mediated by alpha-adrenoreceptors, and both are dependent on intracellular calcium derived from two distinct pools. The reversible alpha-blocker, phentolamine, inhibited NE-induced contractions in the presence and the absence of extracellular calcium with similar activity. After eliminating the phasic component of contraction, NE-induced tonic contractions in calcium-free medium were inhibited by phentolamine with competitive kinetics, with a resultant shift of the NE ED50 to the right without depression of maximum-induced tension. The irreversible alpha-blocker, phenoxybenzamine, exhibited noncompetitive kinetics, reducing the maximum NE-induced tonic tension without shifting the NE ED50. The KA of NE was 6.0 X 10(-8) M under calcium-free conditions, and corresponded to reported values determined in the presence of extracellular calcium. These findings indicate that the absence of extracellular calcium does not alter the affinity of NE binding to its alpha-receptor, but does create conditions resembling absence or unavailability of spare alpha-receptors.
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D001011:Aorta; D002118:Calcium / Q000502:physiology*; D003470:Culture Media; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009638:Norepinephrine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D010643:Phenoxybenzamine / Q000494:pharmacology; D010646:Phentolamine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000502:physiology
D000317:Adrenergic alpha-Antagonists; D003470:Culture Media; D011942:Receptors, Adrenergic, alpha; D010643:Phenoxybenzamine; D002118:Calcium; D009638:Norepinephrine; D010646:Phentolamine