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.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
REFERENCES
A. Bonz, M. Laser, S. Kullmer, et al., J. Cardiovasc. Pharmacol., 41, No.4, 657–664 (2003).
M. Bouaboula, N. Desnoyer, P. Carayon, et al., Mol. Pharmacol., 55, 473–480 (1999).
M. Bouaboula, S. Perrachon, L. Milligan, et al., J. Biol. Chem., 272, 22,330–22,339 (1997).
T. Costa and A. Herz, Proc. Natl. Acad. Sci. USA, 86, 7321–7325 (1989).
W. R. Ford, S. A. Honan, R. White, and C. R. Hiley, Br. J. Pharmacol., 135, No.5, 1191–1198 (2002).
W. S. Ho and C. R. Hiley, Ibid., 139, No.3, 585–597 (2003).
A. C. Howlett, F. Barth, T. I. Bonner, et al., Pharmacol. Rev., 54, No.2, 161–202 (2002).
R. S. Mansbach, C. C. Rovertti, E. N. Winston, and J. A. Lowe, Psychopharmacology, 124, 315–322 (1996).
L. Maslov and Y. B. Lishmanov, Clinical Exp. Pharmacol. Physiol., 22, 812–816 (1995).
R. Mechoulam, J. J. Feigenbaum, N. Lander, et al., Experientia, 44, 762–764 (1984).
S. Mukhopadhyay, J.-Y. Shim, A. A. Assi, et al., Chem. Physics Lipids, 121, 91–109 (2002).
R. G. Pertwee, Current Med. Chem., 6, 635–664 (1999).
P. L. Prather, Sci. STKE, 215 (2004).
J. A. Wagner, K. Hu, J. Karcher, et al., Br. J. Pharmacol., 138, No.7, 1251–1258 (2003).
Author information
Authors and Affiliations
Corresponding author
Additional information
__________
Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 139, No. 5, pp. 512–516, May, 2005
Rights and permissions
About this article
Cite this article
Krylatov, A.V., Maslov, L.N., Lasukova, O.V. et al. Cannabinoid Receptor Antagonists SR141716 and SR144528 Exhibit Properties of Partial Agonists in Experiments on Isolated Perfused Rat Heart. Bull Exp Biol Med 139, 558–561 (2005). https://doi.org/10.1007/s10517-005-0344-9
Received:
Issue Date:
DOI: https://doi.org/10.1007/s10517-005-0344-9