α(2)-adrenoceptor agonist-induced inhibition of gastric motor activity is mediated by α(2A)-adrenoceptor subtype in the mouse

• Published in: Neurochemistry international 2011-05, Vol.58 (6), p.708-713
• Main Authors: Shujaa, N, Al-Khrasani, M, Zádori, Z S, Rossi, M, Mátyus, P, Németh, J, Hein, L, Gyires, K
• Format: Article
• Language: English
• Subjects: Adrenergic alpha-Agonists - pharmacology; Animals; Clonidine - analogs & derivatives; Clonidine - pharmacology; Mice; Mice, Inbred C57BL; Motor Activity - drug effects; Receptors, Adrenergic, alpha-2 - drug effects; Stomach - drug effects; Stomach - physiology
• ISSN: 1872-9754
• DOI: 10.1016/j.neuint.2011.02.011

The role of α(2)-adrenoceptors in regulation of gastric motility has been well documented. However, only few data are available on the adrenoceptor subtype that mediates this effect. The purpose of the present work was to identify the α(2)-adrenoceptor subtype(s) responsible for the inhibition of gastric motor activity in isolated fundus strip of the mouse. It was shown that (i) the electrically evoked contraction of the gastric fundus strip of the mouse was inhibited by the non-selective α(2)-adrenoceptor stimulant clonidine (EC(50): 0.019±0.001μM), the α(2A)-adrenoceptor subtype selective agonist oxymetazoline (EC(50): 0.004±0.001μM) and the α(2B)-adrenoceptor subtype preferring ST-91 (EC(50): 0.029±0.004μM), (ii) the inhibitory effect of clonidine (1μM), oxymetazoline (0.1μM) and ST-91 (1μM) on the contractions of gastric fundus strip was reversed by the non-selective α(2)-adrenoceptor antagonist idazoxan and α(2A)-adrenoceptor antagonist BRL 44408, but not by the α(2B/2C)-adrenoceptor antagonist ARC-239. (iii) Clonidine and ST-91 inhibited the electrically induced gastric contractions in C57BL/6 wild type mice as well as in α(2B)- and α(2C)-adrenoceptor deficient mice in a concentration-dependent manner; however, neither of them was effective in α(2A)-deficient mice. As a conclusion, it was first demonstrated that the inhibitory effect of α(2)-adrenoceptor agonists on the gastric motor activity of isolated stomach strip of the mouse is mediated purely by α(2A)-adrenoceptors.