Interaction of calcitonin gene-related peptide (CGRP), substance P (SP) and conventional autonomic agonists in rat submandibular salivary peroxidase release in vitro

Our previous immunohistochemical studies reveal that several neuropeptides, such as substance P and calcitonin gene-related peptide, innervate the major salivary glands of the mouse, rat and human. The aim of the study was to clarify their interactions by measuring their effects alone or with conventional autonomic agonists (carbachol, phenylephrine and isoproterenol) on peroxidase secretion of incubated submandibular gland slices. Calcitonin gene-related peptide evoked significant increase in peroxidase activity of the secretion only when used at 10−5 M concentration, while substance P evoked significant, dose-dependent increase at much lower concentrations (10−10 M). Adrenergic and cholinergic agonists enhanced peroxidase activity. Interestingly, substance P inhibited both phenylephrine and isoproterenol induced increase in peroxidase activity. Calcitonin gene-related peptide did not affect the inhibition caused by substance P. Our results demonstrate that in the salivary gland tissue substance P alone or in conjunction with adrenergic agonists result in opposing secretory responses with the doses used in vitro. Conversely, the response mediated by adrenergic receptors may be critically affected by simultaneous occupation of substance P receptors.