Submitted on September 24, 2002
Accepted on March 18, 2003
PERISTALSIS REGULATION BY TACHYKININ NK1 RECEPTORS IN THE RABBIT ISOLATED DISTAL COLON
Luciano Onori1*, Annalisa Aggio1, Gennaro Taddei1, Maria F. Loreto1, Rachele Ciccocioppo1, Riccardo Vicini2, and Marcello Tonini2
1 Department of Internal Medicine and Public Health, University of l'Aquila, L'Aquila, Italy
2 Department of Physiological and Pharmacological Sciences, University of Pavia, Pavia, Italy
* To whom correspondence should be addressed. E-mail: annaggio{at}katamail.com.
In the gastrointestinal tract, tachykinin NK1 receptors are widely distributed in a number of neuronal and non-neuronal cells involved in the control of gut motor activity. In particular, in the rabbit isolated distal colon, which is a suitable model system to investigate the contribution of tachykinins as non-cholinergic excitatory transmitters, the influence of NK1 receptors in the regulation of peristalsis is not known. The selective NK1 receptor antagonists SR140333 (0.3 and 1 nM) and MEN10930 (0.3-10 nM) significantly enhanced the velocity of rabbit colonic propulsion to submaximal stimulation. The prokinetic effect of SR140333 was prevented by L-NNA, a nitric oxide synthase inhibitor, indicating that NK1 receptors located on nitrergic innervation exert a functional inhibitory restraint on the circular muscle and probably on descending excitatory and inhibitory pathways during propulsion. Conversely, the selective NK1 receptor agonist, septide (3-10 nM), significantly inhibited colonic propulsion. In the presence of L-NNA, the inhibitory effect of septide was reverted into a prokinetic effect, which is probably mediated by the activation of postjunctional excitatory NK1 receptors.
