Role for NK(1) and NK(2) receptors in the motor activity in mouse colon

Area of Science:

• Gastroenterology
• Neuropharmacology
• Cellular Physiology

Background:

• Tachykinins, such as substance P and neurokinin A, play roles in gastrointestinal function.
• Neurokinin (NK) receptors, specifically NK1 and NK2, are implicated in modulating colonic motility.
• Understanding the precise roles and localization of these receptors is crucial for comprehending colonic mechanical activity.

Purpose of the Study:

• To investigate the functional roles of endogenous and exogenous activation of NK1 and NK2 receptors in mouse proximal colon mechanical activity.
• To determine the localization of NK1 and NK2 receptors within the colonic tissue.
• To elucidate the contribution of these receptors to nonadrenergic noncholinergic (NANC) contractions.

Main Methods:

• In vitro experiments using isolated mouse proximal colon segments.
• Measurement of intraluminal pressure changes to assess mechanical activity.
• Pharmacological manipulation using selective receptor agonists and antagonists (SR140333 for NK1, SR48968 for NK2), electrical field stimulation, tetrodotoxin, atropine, and L-NAME.

Main Results:

• Electrical field stimulation induced NANC contractions, significantly reduced by NK1 and NK2 antagonists, with NK2 antagonists showing greater efficacy.
• Selective NK1 receptor agonist ([Sar(9), Met(O(2))(11)]-substance P) caused a biphasic response (contraction then inhibition), while the selective NK2 agonist ([beta-Ala(8)]-neurokinin A (4-10)) induced concentration-dependent contraction.
• NK1 receptor activation involved cholinergic and nitrergic neurons and smooth muscle cells, whereas NK2 receptor activation appeared restricted to smooth muscle cells.

Conclusions:

• Both NK1 and NK2 receptors are activated by endogenous tachykinins in the mouse colon, contributing additively to mechanical activity.
• NK1 receptors are located on cholinergic and nitrergic neurons, as well as smooth muscle cells.
• NK2 receptors are exclusively found on smooth muscle cells, mediating contractions.