Inhibition by amiloride and by Na+-depletion of A23187-stimulated arachidonic acid and histamine release from rat mast cells.
Rat peritoneal mast cells, labelled with [14C]arachidonic acid, released histamine and [14C]arachidonic acid upon the addition of A23187. The release induced by low concentrations of A23187 was suppressed by removal of extracellular Na+ and by addition of the Na+/H+ exchange inhibitor, amiloride. Addition of protein kinase C inhibitors resulted in only a modest decrease of [14C]arachidonic acid and histamine release. [14C]Arachidonic acid was hydrolyzed from both phosphatidylcholine and triacylglycerol. Amiloride inhibited only the hydrolysis from phosphatidylcholine. It is suggested that an Na+/H+ exchange is stimulated secondary to an A23187-induced increase in intracellular calcium concentration. Increased Na+/H+ exchange seems to facilitate the activation by intracellular calcium ions of phospholipase A2 as well as of histamine secretion.
Linnebjerg
H
H
PharmaBiotec Research Center, Royal Danish School of Pharmacy, Copenhagen.
Hansen
H S
HS
Jensen
B
B
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000584:Amiloride / Q000494:pharmacology*; D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism*; D000001:Calcimycin / Q000494:pharmacology; D002352:Carrier Proteins / Q000502:physiology; D006636:Histamine Release / Q000187:drug effects*; D066298:In Vitro Techniques; D007546:Isoquinolines / Q000494:pharmacology; D008407:Mast Cells / Q000187:drug effects* / Q000502:physiology; D010879:Piperazines / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D051381:Rats; D012964:Sodium / Q000172:deficiency*; D017923:Sodium-Hydrogen Exchangers; D013110:Sphingosine / Q000494:pharmacology
D001095:Arachidonic Acids; D002352:Carrier Proteins; D007546:Isoquinolines; D010879:Piperazines; D017923:Sodium-Hydrogen Exchangers; D016718:Arachidonic Acid; D000001:Calcimycin; D000584:Amiloride; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D012964:Sodium; D011493:Protein Kinase C; D013110:Sphingosine