Norepinephrine-sensitive, phenoxybenzamine-resistant receptor sites associated with contraction in rabbit arterial but not venous smooth muscle: possible role in adrenergic neurotransmission.
The possibility that not all contractions of rabbit blood vessels to norepinephrine (NE) are mediated through alpha adrenoceptors sensitive to phenoxybenzamine (PBZ) was investigated. Dose-response curves (DRCs) to NE were made in the absence and presence of PBZ pretreatment which minimized the contribution of alpha adrenoceptors. In all arteries studied (saphenous, renal, femoral and central ear arteries), after PBZ-treatment, NE produced biphasic DRCs. The initial component of these DRCs corresponded to doses of NE which in the absence of PBZ were supramaximal. Under conditions of our experimentation the plateau-phase usually occurred at between 5 and 40% of the pre-PBZ maximal response to NE. The second phase occurred with further additions of NE, and achieved a mean of 72 (+/- 4)% of the pre-PBZ maximal contraction to NE. The latter component presumably represented contractions mediated through low-affinity sites for NE which were insensitive to doses of PBZ sufficient to alkylate alpha adrenoceptors. In veins (saphenous and inferior vena cava), we found no evidence for such sites. Our results are discussed in light of current ideas of adrenergic neurotransmission in vascular smooth muscle as proposed by Hirst and Neild (1980a) and others who suggest that response to high concentrations of neuronally released NE occur through PBZ-resistant receptors termed gamma adrenoceptors located exclusively at the postsynaptic membrane. We were able to demonstrate PBZ-resistant, low-affinity sites for NE contractions in the femoral artery, a vessel with very sparse adrenergic innervation, and conclude that such sites for NE are present in a number of arteries (and not veins) irrespective of their innervation.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D001158:Arteries / Q000032:analysis / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000032:analysis*; D009638:Norepinephrine / Q000494:pharmacology*; D010643:Phenoxybenzamine / Q000494:pharmacology*; D011817:Rabbits; D011942:Receptors, Adrenergic, alpha / Q000032:analysis / Q000187:drug effects* / Q000502:physiology; D013237:Stereoisomerism; D013564:Sympathetic Nervous System / Q000502:physiology*; D009435:Synaptic Transmission; D014661:Vasoconstriction; D014680:Veins / Q000032:analysis / Q000502:physiology
D011942:Receptors, Adrenergic, alpha; D010643:Phenoxybenzamine; D009638:Norepinephrine