Nitrergic transmission: nitric oxide as a mediator of non-adrenergic, non-cholinergic neuro-effector transmission.
1. The possibility that transmission at some non-adrenergic, non-cholinergic (NANC) neuro-effector junctions is mediated by nitric oxide (NO) arose from the discoveries that NO mediated the effects of nitrovasodilator drugs and that endothelium-derived relaxing factor (EDRF) was NO or a NO-yielding substance. 2. NO donated by nitrovasodilator drugs or formed by endothelial cells activates soluble guanylate cyclase in smooth muscle and the consequent increase in cyclic guanosine monophosphate (cGMP) results in relaxation. The relaxations produced by stimulation of some NANC nerves are also due to a rise in cGMP. 3. The biosynthesis of NO by oxidation of a terminal guanidino nitrogen of L-arginine is inhibited by some NG-substituted analogues of L-arginine. These substances block EDRF formation by NO synthase and endothelium-dependent vasodilatation, and the blockade is overcome by L-arginine 4. NANC relaxations in some tissues are blocked by NG-substituted analogues of L-arginine and restored by L-arginine. Other agents that affect endothelium-dependent vasodilator responses produce corresponding changes in responses to stimulation of these NANC nerves. Such observations indicate that transmission is mediated by NO: we have termed this mode of transmission nitrergic. 5. There is evidence for nitrergic innervation of smooth muscle in the gastrointestinal tract, genito-urinary system, trachea and some blood vessels (penile and cerebral arteries). 6. The recognition of a mediator role for NO in neurotransmission calls for reconsideration of previously accepted generalizations about mechanisms of transmission. 7. Studies on nitrergic transmission will provide new insights into physiological control mechanisms and pathophysiological processes and may lead to new therapeutic developments.
Rand
M J
MJ
Department of Pharmacology, University of Melbourne, Victoria, Australia.
D000818:Animals; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D009584:Nitrogen / Q000502:physiology*; D017981:Receptors, Neurotransmitter / Q000502:physiology; D009435:Synaptic Transmission / Q000502:physiology*
D017981:Receptors, Neurotransmitter; D009569:Nitric Oxide; D009584:Nitrogen