Selective cannabinoid receptor agonist HU-210 decreases pump function of isolated perfused heart: Role of cAMP and cGMP
- 57 Downloads
The rate and strength of heart contractions decreased after 10-min perfusion of rat myocardium with Krebs—Henseleit solution containing a selective cannabinoid receptor agonist HU-210 in a final concentration of 10 nM. HU-210 completely blocked the positive inotropic and chronotropic effect of β-adrenoceptor agonist isoproterenol, decreased the basal level of cAMP, and abolished the isoproterenol-induced increase in myocardial cAMP concentration. cGMP concentration remained unchanged under these conditions. The decrease in myocardial cAMP concentration after activation of cannabinoid receptors did not correlate with changes in the strength and rate of heart contractions. Our results suggest that the negative inotropic and chronotropic effects of HU-210 are not associated with decreased cAMP concentration in the myocardium.
Key Wordscannabinoid receptors isolated heart cAMP cGMP
Unable to display preview.
- 1.I. Cavero, M. F. Lokhandwala, J. P. Buckley, and B. S. Jandhyla, Eur. J. Pharmacol., 29, No.1, 74–82 (1974).
- 2.C. C. Felder, J. S. Veluz, H. L. Williams, et al., Mol. Pharmacol., 42, 838–845 (1992).
- 3.A. C. Howlett, T. M. Champion, G. H. Wilker, and R. Mechoulam, Neuropharmacology, 29, No.2, 161–165 (1990).
- 4.B. R. Martin, S. P. Welch, and M. Abood, Advances in Pharmacology, New York (1995), pp. 342–397.
- 5.L. N. Maslov and Yu. B. Lishmanov, Clin. Exp. Pharmacol. Physiol., 22, 812–816 (1995).
- 6.R. Mechoulam, J. J. Feigenbaum, N. Lander, et al., Experientia, 44, 762–764 (1984).
- 7.S. Mukhopadhyay, J.-Y. Shim, A. A. Assi, et al., Chem. Physics Lipids, 121, 91–109 (2002).
- 8.R. G. Pertwee, Curr. Med. Chem., No. 6, 635–664 (1999).
- 9.D. Shire, C. Carrillon, M. Kaghad, et al., J. Biol. Chem., 270, No.8, 3726–3731 (1995).
- 10.K. A. Smiley, R. Karler, and S. A. Turkanis, Res. Commun. Chem. Pathol. Pharmacol., 14, 659–675 (1976).
- 11.H. Vidrio, M. A. Sanchez-Salvatori, and M. Medina, J. Cardiovasc. Pharmacol., 28, 332–336 (1996).