Elevation of intracellular cAMP by noradrenaline and vasoactive intestinal peptide in striated ducts isolated from the rabbit mandibular salivary glands

Abstract

Salivary gland intralobular ducts are responsible for the modification of the electrolyte composition of the primary fluid secreted by the acini. However, the intracellular messengers that regulate this and other intralobular duct cell processes have not been fully characterized. To investigate the possibility that cAMP-mobilizing agonists may be involved, intralobular (striated) ducts were isolated from the rabbit mandibular salivary gland by tissue dissociation and microdissection and maintained in tissue culture overnight. Individual duct fragments were stimulated with the secretory agonists noradrenaline, vasoactive intestinal peptide (VIP) and substance P and their cAMP content measured by acetylated radioimmunoassay. Both noradrenaline and VIP elevated intracellular cAMP content concentration dependently, but substance P did not. The response to noradrenaline was blocked by the β-adrenoceptor antagonist propranolol, but not by the α-adrenoceptor antagonist prazosin. Application of the VIP analogue [ d-ϱ-Cl-Phe 6, Leu 17]-VIP decreased the VIP-induced cAMP response. These results demonstrate that striated intralobular duct cells possess β-adrenoceptors and peptidergic receptors that are coupled to adenylate cyclase and activated by noradrenaline and VIP, respectively. By elevating ductal cAMP content, these agonists may regulate both the electrolyte content of the primary saliva and the secretion of protein(s) from the ducts.