Tachykinins in the gut. Part II. Roles in neural excitation, secretion and inflammation

• Published in: Pharmacology & therapeutics (Oxford) 1997, Vol.73 (3), p.219-263
• Main Authors: Holzer, Peter, Holzer-Petsche, Ulrike
• Format: Article
• Language: English
• Subjects: Animals; Digestive System - blood supply; Digestive System - innervation; Digestive System Physiological Phenomena; enteric nervous system; Gastric Mucosa - blood supply; Gastric Mucosa - innervation; Gastric Mucosa - secretion; Gastrointestinal Diseases - drug therapy; Gastrointestinal Diseases - etiology; Gastrointestinal Diseases - physiopathology; Humans; inflammatory bowel disease; Intestinal Mucosa - blood supply; Intestinal Mucosa - innervation; Intestinal Mucosa - secretion; intestinal secretion; neurokinin A; Neurokinin A - physiology; Neurokinin A - therapeutic use; Neurons, Afferent - cytology; Neurons, Afferent - physiology; Pancreas - secretion; primary afferent neurons; Receptors, Tachykinin - metabolism; Regional Blood Flow - physiology; Saliva - secretion; Signal Transduction - physiology; Substance P; Substance P - physiology; Substance P - therapeutic use; Synaptic Transmission - physiology
• ISSN: 0163-7258; 1879-016X
• DOI: 10.1016/S0163-7258(96)00196-9

The preprotachykinin-A gene-derived peptides substance (substance P; SP) and neurokinin (NK) A are expressed in intrinsic enteric neurons, which supply all layers of the gut, and extrinsic primary afferent nerve fibers, which innervate primarily the arterial vascular system. The actions of tachykinins on the digestive effector systems are mediated by three different types of tachykinin receptor, termed NK 1, NK 2 and NK 3 receptors. Within the enteric nervous system, SP and NKA are likely to mediate, or comediate, slow synaptic transmission and to modulate neuronal excitability via stimulation of NK 3 and NK 1 receptors. In the intestinal mucosa, tachykinins cause net secretion of fluid and electrolytes, and it appears as if SP and NKA play a messenger role in intramural secretory reflex pathways. Secretory processes in the salivary glands and pancreas are likewise influenced by tachykinins. The gastrointestinal arterial system may be dilated or constricted by tachykinins, whereas constriction and an increase in the vascular permeability are the only effects seen in the venous system. Various gastrointestinal disorders are associated with distinct changes in the tachykinin system, and there is increasing evidence that tachykinins participate in the hypersecretory, vascular and immunological disturbances associated with infection and inflammatory bowel disease. In a therapeutic perspective, it would seem conceivable that tachykinin antagonists could be exploited as antidiarrheal, anti-inflammatory and antinociceptive drugs.