cyclic-gmp and tetrapentylammonium

The results of the present study show that human platelets take up l-arginine by two transport systems which are compatible with the systems y+ and y+L. These Na+independent transporters have been distinguished by treating platelets with N-ethylmaleimide that blocks selectively system y+. System y+, that accounts for 30-40% of the total transport, is characterized by low affinity for l-arginine, is unaffected by l-leucine, is sensitive to changes of membrane potential and to trans-stimulation. The other component of l-arginine transport identified with the system y+L (approximately 60-70% of the total flux) shows high affinity for l-arginine, is insensitive to N-ethylmaleimide treatment, unaffected by changes in membrane potential, sensitive to trans-stimulation and inhibited by l-leucine in the presence of Na+. Moreover a strict correlation between l-arginine transport and nitric oxide (NO) production in whole cells was found. N-ethylmaleimide and l-leucine decreased NO production as well as cGMP elevation, and the effect on NO and cGMP were closely related. It is likely that the l-arginine transport systems y+ and y+L are both involved in supplying substrate for NO production and regulation in human platelets.

Topics: Anti-Bacterial Agents; Arginine; Biological Transport; Blood Platelets; Cyclic GMP; Enzyme Inhibitors; Ethylmaleimide; Gramicidin; Humans; Ionophores; Leucine; Membrane Transport Proteins; Nitric Oxide; Quaternary Ammonium Compounds; Sodium; Valinomycin

Quaternary ammonium ions are common pharmacological blockers of K+ channels. This study examined the vasorelaxant effect of tetraoctylammonium ions (TOA+) in rat isolated aortic rings. TOA+ caused a concentration-dependent transient relaxation of endothelium-intact tissues. Pretreatment with NG-nitro-L-arginine methyl ester (L-NAME, 3x10(-5) M) or methylene blue (3 x 10(-6) M) or removal of the endothelium abolished the TOA+-induced relaxation. L-arginine (10(-3) M ) partially antagonized the effect of L-NAME. Glibenclamide (3x10(-6) M), charybdotoxin (CTX, 10(-7) M), indomethacin (10(-5) M), or atropine (3x10(-6) M) had no effect. Both TOA+ (10(-5) M)- and acetylcholine (ACh, 10(-5) M)-induced increase in tissue content of cyclic GMP was significantly attenuated by NG-nitro-L-arginine (L-NNA, 10(-4) M) and abolished in endothelium-denuded arteries. These results indicate that TOA+ induced endothelium-dependent relaxation which is likely mediated through nitric oxide but not other endothelium-derived factors. This relaxant action seems unique for TOA+ since other quaternary ammonium ions did not cause nitric oxide-dependent relaxation.

Topics: Animals; Aorta; Cyclic GMP; Endothelium, Vascular; In Vitro Techniques; Male; Nitric Oxide; Potassium Channel Blockers; Quaternary Ammonium Compounds; Rats; Rats, Sprague-Dawley; Vasodilation; Vasodilator Agents