The modulatory effects of leukotrienes C 4 and D 4 on methacholine- and substance P-induced salivary secretion in rats

Abstract

Although certain prostaglandins have been found to be inhibitory to nerve-evoked salivary flow, little is known of the effects the leukotrienes on salivary secretion. It was the purpose of this investigation to examine the effects of leukotrienes C 4 (LTC 4) and D 4 (LtD 4) on salivary secretion in the rat, using methacholine or substance P to induce basal secretion, and to test whether or not the observed effects of these eicosanoids were receptor-mediated by using the leukotriene receptor blocker FPL-55712. Methacholine (3 × 10 −4 M), or substance P (1 × 10 −6 M) was infused intra-arterially to stimulate secretion and saliva was collected separately from the parotid gland and the submandibular gland of anesthetized rats. LTC 4 and LTD 4 (each at 1 × 10 −9 to 1 × 10 −6 M) were found to reduce methacholine- and substance P-induced salivary flow in a dose-related manner. Salivary protein concentration and amylase activity were not significantly altered by the leukotrienes; however, arginine-esterase activity, stimulated by substance P, was increased by both leukotrienes. FPL-55712 (1 × 10 −8 M) was shown to reduced the inhibitory effects of LTC 4 and LTD 4, suggesting the involvement of leukotriene receptors for these agents in their action.