Nitric oxide as a multimodal transmitter in the brain: discovery and current status

Nitric oxide (NO) operates throughout the brain as an intercellular messenger, initiating its varied physiological effects by activating specialized guanylyl cyclase ‐coupled receptors, resulting in the formation of cGMP. In line with the widespread expression of this pathway, NO participates in numerous different brain functions. This review gives an account of the discovery of NO as a signalling molecule in the brain, experiments that originated in the searc h for a mysterious cGMP‐stimulating factor released from central neurones when their NMDA receptors were stimulated, and summarises the subsequent key steps that helped cement its status as a central transmitter. Currently, various modes of operation are viewed to underlie its diverse behaviour, r anging from very local signalling between synaptic partners (in the orthograde or retrograde directions) to a volume‐type transmission whereby NO synthesised by multiple synchronous sources summate spatially and temporally to influence intermingled neuronal or non‐neuronal cells, irrespective of anatomical connectivity.
Source: British Journal of Pharmacology - Category: Drugs & Pharmacology Authors: Tags: REVIEW ARTICLE THEMED ISSUE Source Type: research