Guanylate cyclase regulates ileal longitudinal muscle contractions induced by neurogenic nitrergic activity in the rat

• Type: Article in International Scientific Journal
• Date: 2010

Authors

Jorge M A Oliveira (Author) FFUP; Jorge Goncalves (Author) FFUP

Journal

Title: Clinical And Experimental Pharmacology And Physiology

Vol. 37 No. 3

Pages: 375-377

ISSN: 0305-1870

Publisher: Wiley-Blackwell

Indexing

ISI Web of Knowledge - 0 Citations

Scopus - 0 Citations

Scientific classification

FOS: Medical and Health sciences > Basic medicine

Other information

Authenticus ID: P-003-8G9

DOI: 10.1111/j.1440-1681.2009.05271.x

Abstract (EN): P>1. Nitrergic neurons regulate gastrointestinal (GI) activity and their dysfunction has been associated with various GI diseases. Nitric oxide (NO) typically relaxes GI smooth muscle, but nitrergic contractions also occur. Although guanylate cyclase is well established as mediating nitrergic GI relaxation, its role in contraction remains uncertain. 2. We used electrical field stimulation (EFS; 0.3 msec pulses, three trains of 1.2 s width, 2 Hz, at 30 s intervals) to evoke biphasic contraction-relaxation responses in rat ileum strips (longitudinal muscle-myenteric plexus preparations), mediated by the endogenous nitrergic transmitter, under non-adrenergic, non-cholinergic (NANC) conditions (1 mu mol/L atropine and 4 mu mol/L guanethidine). 3. All EFS responses were abolished by tetrodotoxin (1 mu mol/L). Inhibition of NO synthase with N omega-nitro-l-arginine-methyl-ester (l-NAME; 100 and 300 mu mol/L) prevented both EFS-evoked contractions and relaxations. l-Arginine (3 mmol/L) reversed l-NAME inhibition, primarily restoring contractions and suggesting that these require lower nitrergic transmitter levels than relaxations. 4. Pretreatment of preparations with subrelaxant concentrations of sodium nitroprusside (1 mu mol/L) selectively desensitized EFS-evoked contractions without affecting relaxations, suggesting different downstream mechanisms. Nevertheless, the selective guanylate cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (3 and 10 mu mol/L) inhibited both nitrergic contractions and relaxations, indicating that guanylate cyclase activation is required for both responses. 5. The results of the present study support the hypothesis that the endogenous nitrergic transmitter differentially regulates guanylate cyclase, leading to either contractions or relaxations depending on its concentrations, thus providing additional insight into the regulation of ileum contractility by nitrergic activity.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 3