Refulation of PAF biosynthesis and its role in salivary secretion

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Platelet-Activating Factor (PAP) was released from a variety of inflammatory and immune-related cells. Moreover, PAF production has been demonstrated in a wider variety of cells and tissues, and suggested that PAF plays various physiological and pathological roles. We have previously shown that PAF is generated upon physiological stimulations in dog salivary gland cells. The present study examined the regulation of PAP biosynthesis and its role in secretory response in salivary glands.1 Acetylcholine (ACh), phenyleprine, isoproterenol and 8Br-cyclic AMP increased lyso-PAP : acetylCoA acetyltransferase (ACT) and DDT-insensiteve cholinephosphotransferase. ACh and phenylephrine increased ACT, and PAP generation in a Ca^2^+-dependent manner.2 PAP receptor expression in salivary glands was studied by examining PAF receptor gene expression using the RT-PCR technique. The specific amplification of PAP receptor-specific PCR fragment from guinea pig, but not dog salivary glands was detected.3 X … More enopus laevis oocytes injected with mRNA from submandibular glands of guinea pig and dogs were electrohysiologically analysed. Application of 1 muM PAP elicited a small current in the oocytes injected with mRNA from guinea pig but not dog submandibular glands.4 PAP stimulated mucin release in the slice of gunea pig submandibular glands.5 PAP is not releasable out of the cells but retained intracellulary in the cells. To assess its intracellular activity, the effect of PAP on Na^+, K^+-ATPase activity in the membrane fraction was examined. PAF inhibited Na^+, K^+-ATPase in the membrane preparations of dog submandibular glands. The inhibitory effect of a low concentration but not of high concentrations of PAP was antagonized by a PAP-receptor antagonists, BN 50739. Kinetic analysis of PAP-induced inhibition of Na^+, K^+-ATPase suggests that the inhibition of Na^+, K^+-ATPase by PAP is not due to competition by PAP at K^+-or Na^+-binding sites on the enzyme, but by complex inhibitory mechanisms.These results suggested that l : PAP biosynthesis is regulated autonomic nerve via remodelling pathway, 2 : PAP receptor is expressed guinea pig salivary gland and functions to stimulate secretory response, 3 : PAP may act as intracellular signal messenger to modulate secretory response in salivary glands. Less