| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Department of Cell Biology, Physiology and Immunology, Universitat Autonoma de Barcelona, Bellaterra, Barcelona, Spain
2 Department of Surgery, Hospital de Mataro, Mataro, Barcelona, Spain
3 Department of Surgery, Hospital de Mataro, Mataro, Barcelona, Spain; Fundacio de Gastroenterologia Dr. F. Vilardell, Barcelona, Barcelona, Spain
* To whom correspondence should be addressed. E-mail: marcel.jimenez{at}uab.es.
Indirect evidence suggests that ATP is a neurotransmitter involved in inhibitory pathways in the neuromuscular junction in the gastrointestinal tract. The aim of this study was to characterize purinergic inhibitory neuromuscular transmission in the human colon. Tissue was obtained from colon resections for neoplasm. Muscle bath, microelectrode experiments and immunohistochemical techniques were performed. MRS 2179 was used as a selective inhibitor of P2Y1 receptors. We found that 1) ATP (1mM) and ADP
S (10 µM), a preferential P2Y agonist, inhibited spontaneous motility and caused smooth muscle hyperpolarization (about -12mV), 2) MRS 2179 (10µM) and apamin (1µM) significantly reduced these effects, 3) both the fast component of the inhibitory junction potential (IJP) and the non-nitrergic relaxation induced by electrical field stimulation were dose-dependently inhibited (IC50 about 1µM) by MRS 2179, 4) ADPS reduced the IJP probably by a desensitization mechanism, 5) apamin (1µM) reduced the fast component of the IJP (by 30%-40%) and the inhibitory effect induced by EFS and 6) P2Y1 receptors were localized in smooth muscle cells as well as in enteric neurons. These results show that ATP or a related purine is released by enteric inhibitory motor neurons causing a fast hyperpolarization and smooth muscle relaxation. The high sensitivity of MRS 2179 has revealed, for the first time in the human gastrointestinal tract, that a P2Y1 receptor present in smooth muscle probably mediates this mechanism through a pathway that partially involves apamin-sensitive calcium-activated potassium channels. P2Y1 receptors can be an important pharmacological target to modulate smooth muscle excitability.
This article has been cited by other articles:
|
|
 |
|
  D. Gallego, V. Gil, J. Aleu, M. Auli, P. Clave, and M. Jimenez Purinergic and nitrergic junction potential in the human colon Am J Physiol Gastrointest Liver Physiol, September 1, 2008; 295(3): G522 - G533. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. McDonnell, R. Hamilton, M. Fong, S. M. Ward, and K. D. Keef Functional evidence for purinergic inhibitory neuromuscular transmission in the mouse internal anal sphincter Am J Physiol Gastrointest Liver Physiol, April 1, 2008; 294(4): G1041 - G1051. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. F. King and A. Townsend-Nicholson Involvement of P2Y1 and P2Y11 Purinoceptors in Parasympathetic Inhibition of Colonic Smooth Muscle J. Pharmacol. Exp. Ther., March 1, 2008; 324(3): 1055 - 1063. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G.-D. Wang, X.-Y. Wang, H.-Z. Hu, S. Liu, N. Gao, X. Fang, Y. Xia, and J. D. Wood Inhibitory neuromuscular transmission mediated by the P2Y1 purinergic receptor in guinea pig small intestine Am J Physiol Gastrointest Liver Physiol, June 1, 2007; 292(6): G1483 - G1489. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Alberti, H. B. Mikkelsen, X. Y. Wang, M. Diaz, J. O. Larsen, J. D. Huizinga, and M. Jimenez Pacemaker activity and inhibitory neurotransmission in the colon of Ws/Ws mutant rats Am J Physiol Gastrointest Liver Physiol, June 1, 2007; 292(6): G1499 - G1510. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. M. Gwynne and J. C. Bornstein Mechanisms underlying nutrient-induced segmentation in isolated guinea pig small intestine Am J Physiol Gastrointest Liver Physiol, April 1, 2007; 292(4): G1162 - G1172. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Visit Other APS Journals Online |
