Acetylcholine-like effects of 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine ('platelet-activating factor') and its analogues in exocrine secretory glands

Abstract

The effect of 1-O-hexadecyl-2-acetyl-sn-glycero-3-phosphocholine (1), 1-O-octadecyl-2-acetyl-sn-glycero-3-phosphocholine (2) 1-O-hexadecyl-sn-glycero-3-phosphocholine (3), 1-O-octadecyl-2-O-methyl-sn-glycero-3-phosphocholine (4) and its enantiomer 3-O-octadecyl-2-O-methyl-sn-glycero-1-phosphocholine (5) on the secretion of amylase from guinea pig isolated parotid gland and exocrine pancreatic lobules was examined. Compounds 1, 2 and 4 led to a significant stimulation of amylase release in both systems, effects being already visible between 10-100 pM. Maximal stimulation with compounds 1 and 2 occurred at 5 nM, with compound 4 at 1 nM. Higher concentrations were less effective and at 0.1 microM stimulation was very low. In contrast, compound 5 showed a continuous increase in activity up to 0.01-0.1 microM without a decrease at at higher concentrations. Compound 3 had no effect. For compound 1, its effects on calcium and lipid metabolism have been analyzed and compared with those of the acetylcholine analogue carbamoylcholine. Compound 1 mimicked in every respect the effects of carbamoylcholine. It stimulated the uptake of 45Ca by isolated parotid gland lobules in a non-ionophoretic way. In isolated pancreatic lobules it enhanced the incorporation of [32P]phosphate into phosphatidic acid, phosphatidylinositol and poly(phosphoinositide), increased the formation of diacylglycerols and triacylglycerol, led to the same two-phasic responses of myo-[3H]inositol-labeled polyphosphoinositides, and initiated a rapid short-lasting formation of free inositol triphosphate. Accordingly, 'platelet activating factor(s)' can affect the function of exocrine glands at low concentrations. The effects observed resemble those produced by acetylcholine and result most likely from the interaction of platelet-activating factor with plasma membrane receptors.