NEURONAL NITRIC-OXIDE IN THE GUT

Motility of the gastrointestinal tract is directly controlled by enter ic inhibitory and excitatory motor neurons that innervate the layers o f smooth muscle. Inhibitory motor neurons mediate receptive and accomm odative relaxations and control the opening of sphincters, thus playin g an important role in normal gut motility. Recent studies have demons trated that nitric oxide (NO) is an important neurotransmitter release d by inhibitory motor neurons in animal and human gut. Antagonists of nitric oxide synthase (NOS), the synthetic enzyme for NO, reduce the e ffectiveness of transmission from inhibitory motor neurons. Exogenous NO mimics inhibitory nerve activation, and a variety of compounds that affect the availability of endogenously produced NO modulate relaxati ons of gastrointestinal smooth muscle. It is clear, however, that NO i s unlikely to be the only transmitter released by enteric inhibitory m otor neurons: several other substances such as vasoactive intestinal p olypeptide (VIP), or related peptides, and adenosine triphosphate (ATP ) are also likely to contribute to nerve-mediated inhibition. The iden tification of NO as a major inhibitory neurotransmitter to gastrointes tinal smooth muscle fills an important gap in our understanding of the physiological control of motility and opens up a wide range of new ex perimental possibilities. It may eventually lead.to the development of new drugs for motility disorders. It should be noted, however, that N O is important in the brain, in cardiovascular control, in blood cell function and in many other organ systems, suggesting that it may be di fficult to achieve specific pharmacological intervention targeted on i nhibitory neurotransmission in the gut, without undesirable side effec ts.