TACHYKININ RECEPTORS AND INTESTINAL MOTILITY

Substance P (SP) and neurokinin A (NKA) are synthesized by enteric cho linergic motorneurons that project to the longitudinal and circular mu scle of the mammalian intestine. Thus, acetylcholine, SP, and NKA are the excitatory neuromuscular transmitters in the intestine. Tachykinin NK1 and NK2 receptors are expressed by smooth muscle cells in most re gions of the intestine: the corelease of SP and NKA from nerves thus r ealizes paradigms of tachykininergic cotransmission. Examples have bee n found in which a cooperative model can be applied to account for the action of SP-NKA acting at NK1 and NK2 receptors (e.g., circular musc le of guinea-pig duodenum), as well as examples in which the message p roduced by activation of the two receptors diverges sharply in produci ng responses that have a markedly different time course and use differ ent effector systems (e.g., circular muscle of guinea-pig colon). NK3 receptors are expressed on both excitatory and inhibitory motor neuron s: indirect contractions (via release of acetylcholine and tachykinins ) and relaxations (via release of nitric oxide) can be evoked in the g ut by selective stimulation of NK3 receptors. Although a role of NK3 r eceptors in certain enteric reflexes has been evidenced, the importanc e of this system in mediating hexamethonium-resistant enteric transmis sion appears less important than previously speculated.