Interaction between PAF and drugs that stimulate formation of inositol phosphates

1. We examined the effect of platelet-activating factor (PAF) on alpha 1-adrenergic and muscarinic cholinergic receptors in the membranes of rat parotid and the functional responses to norepinephrine (NE) and carbamylcholine (CCh) in exocrine secretion. 2. Pretreatment of parotid slices with 1 microM PAF caused a significant decrease the density of [3H]prazosin and [3H]quinuclidinyl benzilate binding sites without a change in the affinity. 3. In functional studies, pretreatment of parotid slices with 1 microM PAF markedly reduced the increase in intracellular 3H-labeling of inositol phosphates induced by NE and CCh. However, the EC50 values for NE and CCh stimulation of [3H]inositol phosphates in 1 microM PAF treated slices were significantly higher when compared to those of controls. 4. In addition, NE- and CCh-induced K+ release from parotid slices were also inhibited by PAF (1 microM) treatment. CV3988, a PAF antagonist, protected against these PAF-induced changes. 5. These results suggests that PAF-induced downregulation of alpha 1-adrenergic and muscarinic cholinergic receptors is mediated through specific PAF receptors in rat parotid glands, and that PAF could be a mediator which alters alpha 1-adrenergic and muscarinic cholinergic responses.