Effects of guanabenz and guanfacine on postsynaptic ?2-adrenoceptors in the rat submaxillary and parotid glands

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Abstract
The effects of two α2-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 μg/kg i.v. produced an immediate and persistent secretion of saliva from the submaxillary gland, guanabenz in doses as high as 40,000 μg/kg did not induce measurable secretion either from the parotid or the submaxillary gland. Secretion clicited by guanfacine was not modified by yohimbine (300 μg/kg) but was abolished by prazosin (100 μg/kg). In both glands, low doses of either guanabenz (10 μg/kg) or guanfacine (100 μg/kg) markedly inhibited the secretory responses induced by noradrenaline, methacholine and substance P, but not that induced by isoprenaline. The inhibition caused by the α2-agonists was greater for noradrenaline than for either methacholine or substance P. Blockade of α2-adrenoceptors with yohimbine (300 μg/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 α2-agonists prevented the inhibitory effects of guanfacine and guanabenz on the response induced by either one of the three sialagogic agents. Guanabenz (10 μg/kg) did not modify the increase in mean blood pressure observed after the different doses of noradrenaline employed to induce salivary secretion. Guanabenz (10 μg/kg) and guanfacine (100 μg/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 α2-adrenoceptors in the submaxillary as well as parotid gland of the rat inhibits secretory responses which are mediated by either muscarine, substance P and α1-receptors and not those elicited by β-adrenoceptors.

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