DIFFERENCES BETWEEN FULL AND PARTIAL ALPHA-ADRENOCEPTOR AGONISTS IN ELICITING PHASIC AND TONIC TYPES OF RESPONSES IN THE LONGITUDINAL SMOOTH-MUSCLE OF THE RAT PORTAL-VEINSCHWIETERT, HR., WILHELM, D., WILFFERT, B. & VANZWIETEN, PA., Aug-1991, In : Naunyn-Schmiedebergs Archives of Pharmacology. 344, 2, p. 206-212 7 p.
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The aim of the present investigation was to study, taking into account both quantitative and qualitative differences, the influence of full and partial alpha-adrenoceptor agonists on spontaneous myogenic activity in the rat portal vein.
We found that the alpha-adrenoceptor agonists cirazoline, adrenaline, noradrenaline, phenylephrine, St 587, Sgd 101/75, B-HT 920 and UK-14,304 could increase the amplitude of the phasic myogenic contractions in the rat portal vein with apparent differences in EC50 and E(max) values. In addition to an increase in phasic myogenic activity, the alpha-adrenoceptor agonists cirazoline, adrenaline, noradrenaline, and phenylephrine were also able (in higher concentrations) to increase the basal tone of the rat portal vein preparation, again with apparent differences in EC50 and E(max) values. Changing the extracellular Ca2+ concentration from 0.9 mmol/l to 2.5 mmol/l had no influence on the phasic character and the concentration range in which St 587 and UK-14,304 increases spontaneous myogenic activity, although changes in amplitude and frequency of the spontaneous myogenic contractions were less pronounced at a higher extracellular Ca2+ concentration (2.5 mmol/l). By the use of Schild analysis with the competitive alpha-adrenoceptor antagonists prazosin (pA2 = 8.74) and 5-methyl-urapidil (pA2 = 8.37), it was established that the contractile responses to St 587 were mediated by the same alpha-1-adrenoceptor subtype as the phasic and tonic type of contraction elicited by phenylephrine as described in a previous study. The concentration-response curve of UK-14,304 was significantly shifted to the right by low concentrations of prazosin (3 nmol/l-30 nmol/l), indicating stimulation of alpha-1-adrenoceptors by UK-14,304 in the rat portal vein. The alpha-adrenoceptor antagonists phenoxybenzamine and chloroethylclonidine irreversibly blocked the contractile responses to St 587. Based on the method of receptor alkylation with phenoxybenzamine an affinity constant was calculated for St 587 (pK(a) = 5.91). Phenoxybenzamine was approximately 1000-fold more potent in inactivating alpha-1-adrenoceptors than chloroethylclonidine.
In conclusion there appeared to be a divergence in the excitation-contraction coupling of alpha-1-adrenoceptors in the rat portal vein, which is reflected by two types of contraction (phasic versus tonic). The extent to which both the phasic and tonic types of concentration are stimulated by agonists depends on the affinity and intrinsic efficacy for each of the receptor-coupled effector pathways. Thus, partial and full agonism can only meaningfully be discussed if confined to one particular effector pathway.
|Number of pages||7|
|Journal||Naunyn-Schmiedebergs Archives of Pharmacology|
|Publication status||Published - Aug-1991|
- RAT PORTAL VEIN, ALPHA-1-ADRENOCEPTORS, FULL AGONISTS, PARTIAL AGONISTS, AORTIC STRIPS, ALPHA-1-ADRENOCEPTOR, SUBCLASSIFICATION, DERIVATIVES, ANTAGONISTS, INVITRO, RESERVE