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Comparison of inhibition by phentolamine, verapamil and cromakalim of noradrenaline and naphazoline responses in rat vas deferens
268
Pharmacological
Research, Vbl. 26, Supplement 1, 1992
FUROXAN ANALOGUES OF PRAZOSIN: NEW SELECTIVE COMPOUNDSFOR THE CHARACTERIZATION OF dl-ADRENER~lC RECEPTOR SUBTYPES. Marco Orsetti and Antonella Di Stile* Istituto di Farmacologia e Farmacognosia e *Dipartimento di Scienza e Tecnologia de1 Farmaco, UniversitP di Torino. Several compounds, derived from prazosin by substitution of the furan ring have been synthetized and tested for with furazan and furoxan systems, c&-adrenergic receptor antagonism. Compared to prazosin, all compounds retained a discrete dd-receptor blocking activity (pA2 on rat isolated thoOur results suggest also that the furacic aorta ranging from a.5 to 9.3). roxan derivatives can discriminate between two subtypes of &A-adrenoceptors (pA2 calculated from the biphasic Schild plots: 8.2 +0.4 and 8.920.2 for and 11.6kO.2 for the phenylfuroxan analothe methylfuroxan and 7.8 f0.3 indicate that the phenylfuroxan derivative shows a gue). These findings large difference of affinity for the two subpopulations of&d-adrenoceptors in the rat aorta and therefore it may be regarded as a true subtype-specific compound. Other functional studies performed with chloroethylclonidine and WB 4101 on different preparations and binding experiments (competition studies on rat cerebral cortex, submaxillary glands and liver membranes) support the hypothesis that the phenylfuroxan analogue of prazosin might be a useful tool for the subclassification of &,-adrenergic receptors and the interpretation of their physiological role(s).
COMPARISON OF INEIIBITION BY PRENTOLAMINE, VERAPAMIL AND CRClMAKALIM OF NORADRENALINE AND NAPBAZOLINE RESPONSES IN RAT VAS DEFERENS Annalisa Barbieri, Cinzia Boselli, Enzo Grana Institute of Pharmacology, University of Pavia - Italy In a previous work we evidenced some differences in types of contractile responses of isolated rat vas deferens to noradrenaline and naphazoline. At the same time we demonstrated that cromakalim (10w7-10 -6 M) inhibited naphazoline-induced contractions and spontaneous activity induced by exwas hardly posure to naphazoline whereas the response to noradrenaline affected (1). The aim of the present study was to go deeply in the analysis of the components of the mechanical responses to noradrenaline and naphazoline of the whole isolated rat vas deferens and of its epididytnal and prostatic portions. Furthermore the inhibitory effect of cromakal.im was compared with that of verapamil and phentolamine. The results obtained support the contention that imidazolines and phenethylamines act via different mechanisms of action. 1) Grana E., research
This
Barbieri A., Zonta F. 1991. Eur.J.Phannacol. was supported by MUPST 60%.
192; 79-84
Pharmacological
Research, Vbl. 26, Supplement 1, 1992
FUROXAN ANALOGUES OF PRAZOSIN: NEW SELECTIVE COMPOUNDSFOR THE CHARACTERIZATION OF dl-ADRENER~lC RECEPTOR SUBTYPES. Marco Orsetti and Antonella Di Stile* Istituto di Farmacologia e Farmacognosia e *Dipartimento di Scienza e Tecnologia de1 Farmaco, UniversitP di Torino. Several compounds, derived from prazosin by substitution of the furan ring have been synthetized and tested for with furazan and furoxan systems, c&-adrenergic receptor antagonism. Compared to prazosin, all compounds retained a discrete dd-receptor blocking activity (pA2 on rat isolated thoOur results suggest also that the furacic aorta ranging from a.5 to 9.3). roxan derivatives can discriminate between two subtypes of &A-adrenoceptors (pA2 calculated from the biphasic Schild plots: 8.2 +0.4 and 8.920.2 for and 11.6kO.2 for the phenylfuroxan analothe methylfuroxan and 7.8 f0.3 indicate that the phenylfuroxan derivative shows a gue). These findings large difference of affinity for the two subpopulations of&d-adrenoceptors in the rat aorta and therefore it may be regarded as a true subtype-specific compound. Other functional studies performed with chloroethylclonidine and WB 4101 on different preparations and binding experiments (competition studies on rat cerebral cortex, submaxillary glands and liver membranes) support the hypothesis that the phenylfuroxan analogue of prazosin might be a useful tool for the subclassification of &,-adrenergic receptors and the interpretation of their physiological role(s).
COMPARISON OF INEIIBITION BY PRENTOLAMINE, VERAPAMIL AND CRClMAKALIM OF NORADRENALINE AND NAPBAZOLINE RESPONSES IN RAT VAS DEFERENS Annalisa Barbieri, Cinzia Boselli, Enzo Grana Institute of Pharmacology, University of Pavia - Italy In a previous work we evidenced some differences in types of contractile responses of isolated rat vas deferens to noradrenaline and naphazoline. At the same time we demonstrated that cromakalim (10w7-10 -6 M) inhibited naphazoline-induced contractions and spontaneous activity induced by exwas hardly posure to naphazoline whereas the response to noradrenaline affected (1). The aim of the present study was to go deeply in the analysis of the components of the mechanical responses to noradrenaline and naphazoline of the whole isolated rat vas deferens and of its epididytnal and prostatic portions. Furthermore the inhibitory effect of cromakal.im was compared with that of verapamil and phentolamine. The results obtained support the contention that imidazolines and phenethylamines act via different mechanisms of action. 1) Grana E., research
This
Barbieri A., Zonta F. 1991. Eur.J.Phannacol. was supported by MUPST 60%.
192; 79-84