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

The effects of two alpha 2-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 micrograms/kg i.v. produced an immediate and persistent secretion of saliva from the submaxillary gland, guanabenz in doses as high as 40,000 micrograms/kg did not induce measurable secretion either from the parotid or the submaxillary gland. Secretion elicited by guanfacine was not modified by yohimbine (300 micrograms/kg) but was abolished by prazosin (100 micrograms/kg). In both glands, low doses of either guanabenz (10 micrograms/kg) or guanfacine (100 micrograms/kg) markedly inhibited the secretory responses induced by noradrenaline, methacholine and substance P, but not that induced by isoprenaline. The inhibition caused by the alpha 2-agonists was greater for noradrenaline than for either methacholine or substance P. Blockade of alpha 2-adrenoceptors with yohimbine (300 micrograms/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 alpha 2-agonists prevented the inhibitory effects of guanfacine and guanabenz on the response induced by either one of the three sialagogic agents. Guanabenz (10 micrograms/kg) did not modify the increase in mean blood pressure observed after the different doses of noradrenaline employed to induce salivary secretion. Guanabenz (10 micrograms/kg) and guanfacine (100 micrograms/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.