Cannabinoid Receptor Antagonists SR141716 and SR144528 Exhibit Properties of Partial Agonists in Experiments on Isolated Perfused Rat Heart |
| |
Authors: | A?V?Krylatov Email author" target="_blank">L?N?MaslovEmail author O?V?Lasukova R?G?Pertwee |
| |
Institution: | (1) Tomsk State Pedagogical University, Tomsk, Russia;(2) Institute of Cardiology, Tomsk Research Center, Siberian Division, Russian Academy of Medical Sciences, Russia;(3) Aberdeen University, Foresthill, Aberdeen, UK |
| |
Abstract: | We studied the effect of selective cannabinoid receptor ligands on contractility of isolated Langendorff-perfused rat heart. It was found that 10-min perfusion of rat heart with a solution containing selective agonist of CB1 and CB2 receptors HU-210 (10 nM) decreased left ventricular developed pressure and maximum rates of contraction and relaxation. However, HU-210 had no effect on heart rate and end-diastolic pressure. Treatment with selective CB1 receptor antagonist SR141716 (1 µM) and selective CB2 receptor antagonist SR144528 (1 µM) decreased left ventricular developed pressure and maximum rates of contraction and relaxation, but had no effect on heart rate and end-diastolic pressure. Ten-minute perfusion of rat heart with a solution containing selective agonist of CB1 and CB2 receptors HU-210 (10 nM) decreased cAMP concentration in the heart. CB receptor antagonists had little effect on cAMP concentration in the heart. The negative inotropic effect of HU-210 and CB receptor antagonists is probably mediated by activation of CB1 receptors. It can be hypothesized that the decrease in heart cAMP concentration is related to stimulation of CB2 receptors. Our results suggest that selective CB receptor antagonists SR141716 and SR144528 in a final concentration of 1 µM exhibit properties of partial CB receptor agonists.__________Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 139, No. 5, pp. 512–516, May, 2005 |
| |
Keywords: | cannabinoid receptors isolated rat heart cAMP HU-210 SR141716 SR144528 |
本文献已被 PubMed SpringerLink 等数据库收录! |
|