The aim of this study was to evaluate the alpha 1-adrenoceptor properties of S.3341, a new alpha-adrenoceptor agonist. Experiments were performed by recording isometric tension of the rat portal vein. pD2 values and apparent intrinsic efficacy of alpha-adrenoceptor agonists (S.3341, norepinephrine, phenylephrine and clonidine) were assessed from cumulative concentration-response curves. Particular attention was paid to the variations in the amplitude of spontaneous contractions and the increase in the tonus of the vein induced by these agonists. The rank order of activity (pD2 values) of these agonists on the amplitude of spontaneous contractions and on the tonus was as follows: norepinephrine greater than or equal to phenylephrine greater than clonidine greater than S.3341. The activity of S.3341 on spontaneous contractions of the vein was found to be of the alpha 1-type only at concentrations higher than 10(-6)M. This concentration-dependent effect was antagonized by prazosin but not by rauwolscine. For concentrations lower than 10(-6)M, S.3341 decreased the amplitude of spontaneous contractions. This effect was not modified by prazosin or rauwolscine and was affected (decreased) after treatment of the vein with 6-hydroxydopamine (6-OHDA). S.3341 was barely able to increase the tonus of the vein, whatever the concentration used. Moreover, S.3341 was able to antagonize the increase in amplitude of spontaneous contraction and tonus of the vein induced by clonidine and phenylephrine. The effect of S.3341 on the slow inward calcium current was also tested and no effect was found, even at high concentrations. The results suggest that in the rat portal vein, S.3341 is a weak partial alpha 1-adrenoceptor agonist which exhibits a quite novel property not related to an adrenergic stimulation or a calcium entry blocking property. The mechanism of this novel effect remains to be elucidated.
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