Cannabinoid receptor antagonists SR141716 and SR144528 exhibit properties of partial agonists in experiments on isolated perfused rat heart

A V Krylatov, L N Maslov, O V Lasukova, R G Pertwee

Research output: Contribution to journalArticle

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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 mu M) and selective CB2 receptor antagonist SR144528 (1 mu M) 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 CBI 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 mu M exhibit properties of partial CB receptor agonists.

Original languageEnglish
Pages (from-to)558-561
Number of pages4
JournalBulletin of Experimental Biology and Medicine
Volume139
Publication statusPublished - 2005

Keywords

  • cannabinoid receptors
  • isolated rat heart
  • cAMP
  • HU-210
  • SR141716
  • SR144528
  • SELECTIVE INVERSE AGONIST
  • PHARMACOLOGY

Cite this

Cannabinoid receptor antagonists SR141716 and SR144528 exhibit properties of partial agonists in experiments on isolated perfused rat heart. / Krylatov, A V ; Maslov, L N ; Lasukova, O V ; Pertwee, R G .

In: Bulletin of Experimental Biology and Medicine, Vol. 139, 2005, p. 558-561.

Research output: Contribution to journalArticle

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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 mu M) and selective CB2 receptor antagonist SR144528 (1 mu M) 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 CBI 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 mu M exhibit properties of partial CB receptor agonists.",
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T1 - Cannabinoid receptor antagonists SR141716 and SR144528 exhibit properties of partial agonists in experiments on isolated perfused rat heart

AU - Krylatov, A V

AU - Maslov, L N

AU - Lasukova, O V

AU - Pertwee, R G

PY - 2005

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N2 - 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 mu M) and selective CB2 receptor antagonist SR144528 (1 mu M) 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 CBI 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 mu M exhibit properties of partial CB receptor agonists.

AB - 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 mu M) and selective CB2 receptor antagonist SR144528 (1 mu M) 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 CBI 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 mu M exhibit properties of partial CB receptor agonists.

KW - cannabinoid receptors

KW - isolated rat heart

KW - cAMP

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KW - SR141716

KW - SR144528

KW - SELECTIVE INVERSE AGONIST

KW - PHARMACOLOGY

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EP - 561

JO - Bulletin of Experimental Biology and Medicine

JF - Bulletin of Experimental Biology and Medicine

SN - 0007-4888

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