Effects of guanabenz and guanfacine on postsynaptic α2-adrenoceptors in the rat submaxillary and parotid glands

M. D. Kaniucki, J. C. Elverdin, F. J. E. Stefano and C. J. Perec

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Abstract

The effects of two agr2-agonists (guanfacine and guanabenz) on both the submaxillary and parotid gland of the rat were studied. Whereas guanfacine in doses ranging between 1,000 and 30,000 mgrg/kg i.v. produced an immediate and persistent secretion of saliva from the submaxillary gland, guanabenz in doses as high as 40,000 mgrg/kg did not induce measurable secretion either from the parotid or the submaxillary gland. Secretion clicited by guanfacine was not modified by yohimbine (300 mgrg/kg) but was abolished by prazosin (100 mgrg/kg).
In both glands, low doses of either guanabenz (10 mgrg/kg) or guanfacine (100 mgrg/kg) markedly inhibited the secretory responses induced by noradrenaline, methacholine and substance P, but not that induced by isoprenaline. The inhibition caused by the agr2-agonists was greater for noradrenaline than for either methacholine or substance P. Blockade of agr2-adrenoceptors with yohimbine (300 mgrg/kg) did not modify the response to noradrenaline, methacholine or substance P in either gland. However, the same dose of yohimbine injected 5 min before the agr2-agonists prevented the inhibitory effects of guanfacine and guanabenz on the response induced by either one of the three sialagogic agents. Guanabenz (10 mgrg/kg) did not modify the increase in mean blood pressure observed after the different doses of noradrenaline employed to induce salivary secretion. Guanabenz (10 mgrg/kg) and guanfacine (100 mgrg/kg) did not change the time course of the secretion elicited by either noradrenaline, methacholine or substance P, since the degree of inhibition was of similar magnitude at all the periods of time analyzed.
The results obtained give further support to the hypothesis that activation of agr2-adrenoceptors in the submaxillary as well as parotid gland of the rat inhibits secretory responses which are mediated by either muscarine, substance P and agr1-receptors and not those elicited by beta-adrenoceptors.

Key words  agr2-Agonists - Salivary secretion - Postsynaptic agr2-adrenoceptors - Guanabenz - Guanfacine

Partially supported by grants no. 3111 k/83 CONICET and Res 40-5/4/84 SUBCYT

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