Theoretical and functional studies on alpha 1-and alpha 2-adrenoreceptors: an examination using the Schild plot.
1 The influence on the shape of the Schild plot by a two-receptor system was studied in both functional and theoretical studies. In the functional studies, the alpha-adrenoreceptors in cat lingual arteries were studied since both alpha 1- and alpha 2-adrenoreceptors have been suggested to contribute to the noradrenaline-induced contractile response in this tissue. 2 The Schild plots constructed using noradrenaline (NA) as agonist and prazosin as antagonist gave a straight line with a slope close to unity. In contrast, the corresponding Schild plot constructed for rauwolscine appeared to be biphasic. 3 The results obtained in the functional study were discussed in view of Schild plots obtained from a theoretical model which was designed to take into consideration the presence of two distinct types of receptor, the percentile proportions of which could be altered. 4 The theoretical model indicates that the shape of the Schild plot can vary considerably depending on the relative contribution of each receptor subtype to the contractile response, the selectivity of the antagonist, and the range and number of antagonist concentrations used. 5 It is suggested that a response is predominantly mediated by alpha 1-adrenoreceptors and less by alpha 2-adrenoreceptors when the Schild plot for prazosin gives a slope close to unity and has a pA2-value representative for alpha 1-adrenoreceptors, and rauwolscine gives a slope less than unity and a significant shift of the NA concentration-response curve in concentrations around 10(-8) M. When the reverse is true (but with a significant shift caused by prazosin already at a concentration around 10(-9) M) the contraction elicited by NA is proposed to be predominantly mediated by alpha 2-adrenoreceptors and less by alpha 1-adrenoreceptors.
Skärby
T V
TV
Department of Clinical Pharmacology, Lund University Hospital, Sweden.
Larsson
B
B
D000818:Animals; D001158:Arteries / Q000187:drug effects; D002415:Cats; D003198:Computer Simulation; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D008954:Models, Biological; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009638:Norepinephrine / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000502:physiology*; D014059:Tongue / Q000098:blood supply
D011942:Receptors, Adrenergic, alpha; D009638:Norepinephrine; D011224:Prazosin