Immunocytochemical analysis of the transport of arginine analogues into nitrergic neurons and other cells in the retina and pituitary

Nitric oxide is formed by the action of nitric oxide synthase upon l-arginine. The efficacy of some exogenously applied arginine analogues in inhibiting nitric oxide synthase and thus nitrergic transmission indicates that neurons producing nitric oxide may possess an arginine transport system. To investigate whether arginine analogues are preferentially transported into nitric oxide-utilising cells or into cells making other neurochemicals, we have raised highly specific antisera against a number of arginine analogues including NG-methyl arginine, D-arginine, NGnitro-L-arginine, NG-nitro-L-arginine methyl ester and canavanine. Retinae were incubated in physiological media containing these analogues and rats were given intraperitoneal injections of the analogues to study the pituitary. Immunocytochemistry and NADPH-diaphorase histochemistry revealed that many of these analogues could be transported preferentially, but not exclusively, into nitric oxide-generating cells. However, some nitric oxide-producing cells apparently lacked the ability to take up some arginine analogues. We conclude that nitric oxide-generating cells in the retina and pituitary possess one or more arginine transporters. Other subsets of neurons that use GABA or glutamate as a neurotransmitter may also accumulate arginine analogues, possibly as a substrate for formation of these neurochemicals.