Mechanisms of the palmitoylcarnitine-induced response in vascular endothelial cells

The mechanisms of Ca2+ mobilization induced by palmitoylcarnitine (Palcar) in rabbit aortic endothelial cells (ETCs) were examined using electrophysio logical techniques. The results obtained were compared with those induced b y acetylcholine (ACh). When a rabbit aortic muscle preparation with an inta ct endothelium was treated with 10 CIM Palcar, the ACh-induced relaxation w as markedly attenuated, whereas endothelium-independent relaxation caused b y sodium nitroprusside was not affected. Under perforated-patch whole-cell- clamp conditions, the application of Palcar over the concentration range 0. 3 and 10 mu M elicited a slowly activating outward current (IPalcar-out), w hereas ACh induced a rapidly activating outward current (I-ACh). A potassiu m channel blocker, 4-aminopyridine, significantly inhibited both IPalcar-ou t and IACh. Removal of external Ca2+ almost abolished IPalcar-out. Under th e same conditions, however, I-ACh remained transient. Addition of cation ch annel blockers SK&F96365 and La3+ inhibited IPalcar-out more effectively th an I-ACh Application of staurosporine, an inhibitor of protein kinase C, af fected neither I-ACh nor IPalcar-out. In contrast, treatment of ETCs with p ertussis toxin (PTX) reduced I-ACh and almost abolished IPalcar-out. These findings demonstrate that, in ETCs, Palcar induces Ca2+ influx via the acti vation of PTX-sensitive GTP-binding protein, leading to the activation of C a2+-dependent K+ current and hyperpolarization of the cell.