NONADRENERGIC NONCHOLINERGIC (NANC) TRANSMISSION TO SMOOTH-MUSCLE - 35 YEARS ON

In 1963, two substances were thought to mediate all transmission betwe en neurons, as well as between nerve and muscle in the peripheral nerv ous system, namely acetylcholine and noradrenaline. This paradigm prim arily was due to the research of Dale, Loewi and von Euler in the firs t half of the century [Dale, 1937 (Transmission of nervous effects by acetylcholine, Harvey Lect. 32, pp. 229-245)]. However, in 1963, a ser ies of experiments were carried out using recently introduced electrop hysiological techniques, which showed unequivocally for the first time that the classical paradigm was not correct. Both inhibitory and exci tatory junctions between nerves and smooth muscle cells were shown to exist in which transmission was mediated by non-adrenergic, non-cholin ergic (NANC) transmitters. In the succeeding 35 years, identification of these NANC transmitters has been a major task of neuropharmacology, with nitric oxide, neuropeptides, and purines being isolated. This re view presents an historical account of the developments this century o f the classical paradigm, of how it was displaced, and of the progress made in identifying the neuromuscular transmitters of the autonomic n ervous system. (C) 1997 Elsevier Science Ltd.