Yohimbine increases submaxillary kallikrein release into the saliva in dogs: evidence for alpha 2-adrenoceptor-mediated inhibition of cholinergic pathways.

1. The effects of the alpha 2-adrenoceptor antagonist, yohimbine (0.5 mg kg-1, i.v.) on basal, sympathetic and parasympathetic stimulation-induced submaxillary kallikrein release were investigated in the anaesthetized dog. Kallikrein was measured by its kininogenase activity before and after trypsin activation which also allowed a study of the proportion of active to total enzyme. 2. Yohimbine induced a rapid, three fold increase in basal kallikrein release correlated with an increase in salivary flow rate which lasted for 60 min following injection. 3. Sectioning the chorda tympani did not affect basal kallikrein release but abolished yohimbine-induced rise in salivary kallikrein secretion. 4. Parasympathetic stimulation alone induced a 3 to 4 fold increase in basal kallikrein release correlated with an increase in salivary flow rate. Yohimbine induced a significant additional increase in parasympathetic-stimulated kallikrein release. 5. When the cervical sympathetic nerve was sectioned the basal kallikrein release decreased by 30 to 40%. 6. Sympathetic stimulation alone also induced a 3 to 4 fold increase in basal kallikrein. This was not correlated with the salivary flow and unaffected by yohimbine. 7. The results indicate that yohimbine increases submaxillary kallikrein release into the saliva by inhibition of presynaptic alpha 2-adrenoceptors located on the chorda tympani nerve endings.