Tachykinin receptors and intestinal motility

Abstract

Substance P (SP) and neurokinin A (NKA) are synthesized by enteric cholinergic motorneurons that project to the longitudinal and circular muscle 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 regions of the intestine: the corelease of SP and NKA from nerves thus realizes paradigms of tachykininergic cotransmission. Examples have been 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 muscle of guinea-pig duodenum), as well as examples in which the message produced by activation of the two receptors diverges sharply in producing responses that have a markedly different time course and use different effector systems (e.g., circular muscle of guinea-pig colon). NK3 receptors are expressed on both excitatory and inhibitory motor neurons: indirect contractions (via release of acetylcholine and tachykinins) and relaxations (via release of nitric oxide) can be evoked in the gut by selective stimulation of NK3 receptors. Although a role of NK3 receptors in certain enteric reflexes has been evidenced, the importance of this system in mediating hexamethonium-resistant enteric transmission appears less important than previously speculated.

Tachykinin Receptor Expression and Function in Human Esophageal Smooth Muscle

“…Few studies have examined the transduction mechanisms underlying tachykinin-evoked smooth muscle contraction and to our knowledge, none of these have investigated human esophageal muscle. Previous studies suggested that Ca 2ϩ influx through L-type Ca 2ϩ channels was critical for tachykinin-evoked contraction in guinea pig, rabbit, and human colonic smooth muscles (Maggi et al, 1997;O'Riordan et al, 2001). In contrast, a major role for Ca 2ϩ stores has been suggested in human sigmoid colon muscle by Cao et al (2000).…”

“…In guinea pig ileum as well as rabbit and human colon, excitation involves influx of extracellular Ca 2ϩ through nifedipinesensitive, L-type Ca 2ϩ channels (Maggi et al, 1997;O'Riordan et al, 2001). In contrast, contractions of human sigmoid colon are less dependent on Ca 2ϩ influx but are abolished by blockade of the sarcoplasmic reticulum Ca ATPase by thapsigargin (Cao et al, 2000).…”

Contractile effect of tachykinins on rabbit small intestine

“…TKs act as neurotransmitters on neurons and cells (such as smooth muscle, secretory epithelium, and glands) in the gastrointestinal tract of mammals [1][2][3] . They are important excitatory neurotransmitters in the enteric nervous system, are involved in the coordination of gastrointestinal motility, and are powerful spasmogens in almost every region of the mammalian intestine [1][2][3][4][5][6] . Substance P (SP), neurokinin A (NKA) and neurokinin B (NKB) are tachykinins derived from two preprotachykinin (PPT) genes [1,[7][8][9][10] .…”

The Neurokinin A Receptor Activates Calcium and cAMP Responses through Distinct Conformational States

“…Tachykinins (substance P, neurokinin A (NKA), and neurokinin B) act as neurotransmitters in the enteric nervous system (14,15), spinal cord, and brain (16 -18). They exhibit preferential binding to three receptor subtypes, NK1, NK2, and NK3, respectively.…”