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This Article Full Text Full Text (PDF) All Versions of this Article: 295/3/G522    most recent 00510.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Web of Science (2) Citing Articles via Google Scholar Google Scholar Articles by Gallego, D. Articles by Jiménez, M. Search for Related Content PubMed PubMed Citation Articles by Gallego, D. Articles by Jiménez, M.

NEUROREGULATION AND MOTILITY

Purinergic and nitrergic junction potential in the human colon

¹Department of Cell Biology, Physiology and Immunology, Universitat Autònoma de Barcelona, Barcelona, Spain; ²Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Barcelona, Spain; and ³Fundació de Gastroenterologia Dr Vilardell and Department of Surgery, Hospital de Mataró, Matero (Barcelona), Spain

Submitted 5 November 2007 ; accepted in final form 30 June 2008

The aim of the present work is to investigate a putative junction transmission [nitric oxide (NO) and ATP] in the human colon and to characterize the electrophysiological and mechanical responses that might explain different functions from both neurotransmitters. Muscle bath and microelectrode techniques were performed on human colonic circular muscle strips. The NO donor sodium nitroprusside (10 µM), but not the P2Y receptor agonist adenosine 5'-O-2-thiodiphosphate (10 µM), was able to cause a sustained relaxation. N^G-nitro-L-arginine (L-NNA) (1 mM), a NO synthase inhibitor, but not 2'-deoxy-N⁶-methyl adenosine 3',5'-diphosphate tetraammonium salt (MRS 2179) (10 µM), a P2Y antagonist, increased spontaneous motility. Electrical field stimulation (EFS) at 1 Hz caused fast inhibitory junction potentials (fIJPs) and a relaxation sensitive to MRS 2179 (10 µM). EFS at higher frequencies (5 Hz) showed biphasic IJP with fast hyperpolarization sensitive to MRS 2179 followed by sustained hyperpolarization sensitive to L-NNA; both drugs were needed to fully block the EFS relaxation at 2 and 5 Hz. Two consecutive single pulses induced MRS 2179-sensitive fIJPs that showed a rundown. The rundown mechanism was not dependent on the degree of hyperpolarization and was present after incubation with L-NNA (1 mM), hexamethonium (100 µM), MRS 2179 (1 µM), and NF023 (10 µM). We concluded that single pulses elicit ATP release from enteric motor neurons that cause a fIJP and a transient relaxation that is difficult to maintain over time; also, NO is released at higher frequencies causing a sustained hyperpolarization and relaxation. These differences might be responsible for complementary mechanisms of relaxation being phasic (ATP) and tonic (NO).

ATP; IJP; smooth muscle; rundown; purinergic receptors