The nervous release and the action of substances which affect intestinal muscle through neither adrenoreceptors nor cholinoreceptors

Mammalian gastrointestinal muscle is supplied by non-adrenergic, intrinsic inhibitory neurons. The substantial evidence which exists to suggest that adenosine triphosphate is the transmitter released from these nerves is discussed briefly. It is shown that the intrinsic inhibitory neurons compose the efferent link in a cascade of descending reflexes extending from the oesophagus to the anal sphincter. Gastrointestinal muscle is also supplied by non-cholinergic excitatory nerves. The pharmacology of transmission from a group of such nerves to the smooth muscle of the guinea-pig proximal colon is described and evidence is presented to suggest that 5-hydroxytryptamine (5-HT) may be the transmitter substance. The contraction is blocked by phentolamine and methysergide which both antagonize the contractile action of 5-HT. When the muscle is desensitized by continued exposure to 5-HT, the noncholinergic contraction can no longer be elicited.