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.
Miyamoto
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A
Department of Pharmacology, Sapporo Medical College, Japan.
Kimura
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H
Ohshika
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H
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002217:Carbachol / Q000494:pharmacology; D066298:In Vitro Techniques; D007294:Inositol / Q000096:biosynthesis; D007295:Inositol Phosphates / Q000096:biosynthesis*; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D010306:Parotid Gland / Q000187:drug effects; D010742:Phospholipid Ethers / Q000494:pharmacology; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D011188:Potassium / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D011813:Quinuclidinyl Benzilate / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects*; D011976:Receptors, Muscarinic / Q000187:drug effects*
D007295:Inositol Phosphates; D010742:Phospholipid Ethers; D010972:Platelet Activating Factor; D011942:Receptors, Adrenergic, alpha; D011976:Receptors, Muscarinic; D007294:Inositol; D011813:Quinuclidinyl Benzilate; C037913:CV 3988; D002217:Carbachol; D011188:Potassium; D002118:Calcium; D009638:Norepinephrine; D011224:Prazosin