Fuel Metabolism as a Determinant of Arachidonic Acid Release and Oxygenation
A variety of stimuli (such as bradykinin, angiotensin, and vasopressin) are believed to interact with cell-surface receptors and evoke a release of arachidonic acid (AA) and its oxygenated metabolites in many cells. One link between the two events is presumed to be the activation of calcium-dependent phospholipases (or possibly calcium-dependent lipoxygenases; Ochi et al.,1983), possibly in some cases via mediation by calmodulin. This Ca2+ might arise from extracellular sources (for example, the calcium influx induced via cell depolarization), in which case the release of the oxygenated products of AA can be blocked by Ca2+ channel blockers (Levine, 1983), or from intracellular stores (blockable by TMB-8, which putatively inhibits release of Ca2+ from intracellular sources; cf. Rittenhouse-Simmons and Deykin, 1978). Alternatively, it has been suggested that receptor occupation can directly activate a phospholipase C, leading to degradation of acidic polyphos-phoinositides. Such breakdown could release membrane-bound Ca2+ (Broekman, 1984), and the concomitant release of inositol phosphates could promote release of Ca2+ from intracellular stores (Streb et al., 1983). Such accumulation of Ca2+ could then potentiate AA release. Whatever the sequence of events leading to arachidonate release in a given cell, the initiating event has usually been considered to take place at the cell surface. In contrast, a possible role for fuel metabolism and related intracellular events in AA release and/or metabolism has received almost no attention. To examine the possibility of such a role, we studied the effect of one fuel (glucose) on the release of the lipoxygenese product 12-hydroxy-eicosatetraenoic acid (12-HETE) from a glucose-sensitive organ, intact rat islets of Langerhans.
KeywordsArachidonic Acid Insulin Secretion Pancreatic Islet Insulin Release Arachidonic Acid Release
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