THE ROLE OF ALPHA-1-ADRENOCEPTOR SUBTYPES IN THE PHASIC AND TONIC RESPONSES TO PHENYLEPHRINE IN THE LONGITUDINAL SMOOTH-MUSCLE OF THE RAT PORTAL-VEIN

The purpose of this investigation was to determine whether alpha-1-adrenoceptor subtypes (co)exist in the rat portal vein and, if so, whether they could be functionally associated with the phasic and tonic types of contraction as a response to alpha-1-adrenoceptor stimulation by phenylephrine.A low Ca2+ concentration (0.9 mmol/l) in the Tyrode solution enabled us to quantify changes both in the phasic myogenic activity and in the basal tone of the rat portal vein preparation very precisely. We used both competitive and non-competitive alpha-adrenoceptor antagonists which have been employed successfully by other investigators to discriminate between alpha-1-adrenoceptor subtypes in vascular and other tissues. Schild analysis showed that the competitive alpha-adrenoceptor antagonists prazosin, phentolamine, yohimbine, corynanthine, idazoxan, rauwolscine and 5-methyl-urapidil could not distinguish between the phasic and tonic responses to phenylephrine and/or different alpha-1-adrenoceptor subtypes in the rat portal vein. However, when we compared our pA2 values with those found to be representative indicators according to subclassifications based on the use of selective antagonists in different tissues, the alpha-1-adrenoceptors in the rat portal vein appeared to belong to the alpha-1L- or alpha-1a- subtype. This subclassification was not in accordance with the data obtained with the irreversible alpha-adrenoceptor antagonist chloroethylclonidine. However, the validity of this alkylating agent as a tool for receptor classification was restricted, at least in the rat portal vein, by its effects on receptor reserve. In contrast to the competitive alpha-adrenoceptor antagonists, the irreversible alpha-adrenoceptor antagonists phenoxybenzamine and chloroethylclonidine could indeed discriminate between the phasic and tonic types of contraction in response to alpha-1-adrenoceptor stimulation by phenylephrine, indicating two different receptor reserves for phenylephrine for the two types of responses.In conclusion, both the phasic and tonic types of contraction elicited by phenylephrine in the longitudinal smooth muscle of the rat portal vein appear to be mediated by one particular alpha-1-adrenoceptor subtype as defined by Schild analysis with selective, competitive alpha-adrenoceptor antagonists. However, using the method of receptor alkylation with phenoxybenzamine, two different affinity constants for the two types of responses could be calculated for phenylephrine. This may reflect the involvement of two different subtypes of alpha-1-adrenoceptors or, more probably, the existence of only one alpha-1-adrenoceptor subtype, which is coupled with two different intrinsic efficacies to the effector pathways mediating the phasic and tonic responses, respectively.