Vasoactive intestinal peptide binding to specific receptors on rat parotid acinar cells induces amylase secretion accompanied by intracellular accumulation of cyclic adenosine 3'-5'-monophosphate

Abstract

Specific binding sites for vasoactive intestinal polypeptide (VIP) were characterized in dispersed rat parotid acini. The binding of [125I]VIP was rapid, saturable, reversible, and temperature dependent. Scatchard analysis indicated two functionally independent classes of receptor sites: 41,000 high affinity-low capacity sites per cell with a dissociation constant (Kd) of 6.4 nM and 420,000 low affinity-high capacity sites per cell with a Kd of 150 nM. A peptide with N-terminal histidine and C-terminal isoleucine and secretin, which are structurally related to VIP, inhibited the tracer binding 30 and 200 times less strongly, respectively, than VIP. Epinephrine and carbachol did not inhibit [125I]VIP binding to parotid acinar cells. VIP stimulated cAMP accumulation in parotid lobules and induced amylase secretion in a dose-dependent manner. A peptide with N-terminal histidine and C-terminal isoleucine and secretin were less potent than VIP regarding cAMP accumulation (1/12 and 1/80 of VIP, respectively) and amylase secretion (1/40 and 1/500 of VIP, respectively). Substance P did not stimulate cAMP accumulation but stimulated amylase secretion more strongly than VIP. These observations clearly demonstrated the presence of VIP receptors coupled to adenylate cyclase system in the rat parotid gland, which plays an important role in the regulation of the amylase secretion. The regulation of parotid function by VIP was independent of the adrenergic or muscarinic regulatory system and of the influence of substance P.