Partial hindrance by beta-adrenoceptors of the antagonism of prazosin against adrenoceptor agonists in rat caecum.
The relaxation of the carbachol-contracted rat isolated caecum by noradrenaline (NA), adrenaline (A) and isoproterenol (I) was investigated, to identify the pharmacological receptors involved. The organs were pretreated with cocaine to block neuronal uptake. The relative potencies of the three agonists were I >> A > or = NA, indicating the presence of beta-adrenoceptors. However, the shift of concentration-response curves by the beta-adrenoceptor antagonist propranolol varied according to the agonist used, suggesting the presence of distorting factors. Initial attempts to verify if alpha-adrenoceptors were involved, by using the alpha-adrenoceptor antagonist prazosin, were unsuccessful, since the shifts of the concentration-response curves were small and were not concentration dependent, leading to Schild lines with slopes significantly lower than unity. When the experiments with prazosin were repeated in the presence of large concentration of propranolol (10(-5) mol/l) to block beta-adrenoceptors, the relative potencies were changed to NA > A > or = I, reflecting the presence of alpha-adrenoceptors. In addition, the shifts induced by prazosin against A lead to Schild lines with slopes not different from 1.0. It is concluded that alpha-adrenoceptors are also present in the caecum, but its presence can only be clearly disclosed after blockade of beta-adrenoceptors. The results are discussed in relation to other situations known to hinder the determination of relative potencies and competitive antagonism, as for instance the removal of agonist from the vicinity of receptors by drug uptake mechanisms.
Smaili
S S
SS
Department of Pharmacology, Escola Paulista de Medicina, São Paulo, Brazil.
Jurkiewicz
N H
NH
Jurkiewicz
A
A
D000322:Adrenergic Agonists / Q000494:pharmacology*; D000818:Animals; D002432:Cecum / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D011224:Prazosin / Q000494:pharmacology*; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D011942:Receptors, Adrenergic, alpha / Q000032:analysis; D011943:Receptors, Adrenergic, beta / Q000032:analysis / Q000187:drug effects*
D000322:Adrenergic Agonists; D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D011433:Propranolol; D011224:Prazosin