Tags

Type your tag names separated by a space and hit enter

Combined stimulation of glucagon-like peptide-1 receptor and inhibition of cannabinoid CB1 receptor act synergistically to reduce food intake and body weight in the rat.
J Physiol Pharmacol. 2011 Aug; 62(4):395-402.JP

Abstract

Pharmacological activation of the glucagon-like peptide-1 (GLP-1) receptor and inhibition of the cannabinoid CB1 receptor were found to reduce food intake and body weight in humans and animals. Since earlier studies revealed that endocannabinoids may interact with other neurotransmitters to affect feeding behavior, we have examined whether a stable GLP-1 agonist, exendin-4 and a CB1 receptor antagonist, AM 251, may reciprocally enhance their inhibitory effects on food consumption in the rat. Additionally, we have tested whether the blockade of the GLP-1 receptor by exendin (9-39) modifies AM 251-dependent effects on energy balance. In a dose-response study, male Wistar rats were injected intraperitoneally with either 1.5-6.0 μg/kg exendin-4, 0.5-2 mg/kg AM 251, 80-320 μg/kg exendin (9-39) or their vehicle and the daily food and water intake as well as body weight changes were monitored two days before and two days after the injection. Exendin-4 at a dose of 3.0 and 6.0 μg/kg and AM 251 at a dose 2 mg/kg decreased significantly 24-hour food intake and body weight. Therefore, in the next study, the effects of lower doses of exendin-4 (1.5 μg/kg) and AM 251 (1.0 mg/kg) administered alone or together on food consumption were compared. As opposed to being injected alone, the co-administration of the two resulted in a marked decrease in both daily food intake and body weight. Exendin (9-39) did not modify the suppressory effect of the highest AM 251 dose on food consumption. Apparently, the effect of AM 251 on the appetite is not mediated by GLP-1. The concomitant stimulation of GLP-1 receptor and blockade of CB1 receptor, however, may act synergistically to inhibit appetite in the rat.

Authors+Show Affiliations

Department of Behavioral Pathophysiology, Institute of General and Experimental Pathology, Medical University of Lodz, Lodz, Poland. ewa.bojanowska@umed.lodz.plNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22100840

Citation

Bojanowska, E, and E Radziszewska. "Combined Stimulation of Glucagon-like Peptide-1 Receptor and Inhibition of Cannabinoid CB1 Receptor Act Synergistically to Reduce Food Intake and Body Weight in the Rat." Journal of Physiology and Pharmacology : an Official Journal of the Polish Physiological Society, vol. 62, no. 4, 2011, pp. 395-402.
Bojanowska E, Radziszewska E. Combined stimulation of glucagon-like peptide-1 receptor and inhibition of cannabinoid CB1 receptor act synergistically to reduce food intake and body weight in the rat. J Physiol Pharmacol. 2011;62(4):395-402.
Bojanowska, E., & Radziszewska, E. (2011). Combined stimulation of glucagon-like peptide-1 receptor and inhibition of cannabinoid CB1 receptor act synergistically to reduce food intake and body weight in the rat. Journal of Physiology and Pharmacology : an Official Journal of the Polish Physiological Society, 62(4), 395-402.
Bojanowska E, Radziszewska E. Combined Stimulation of Glucagon-like Peptide-1 Receptor and Inhibition of Cannabinoid CB1 Receptor Act Synergistically to Reduce Food Intake and Body Weight in the Rat. J Physiol Pharmacol. 2011;62(4):395-402. PubMed PMID: 22100840.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Combined stimulation of glucagon-like peptide-1 receptor and inhibition of cannabinoid CB1 receptor act synergistically to reduce food intake and body weight in the rat. AU - Bojanowska,E, AU - Radziszewska,E, PY - 2011/06/10/received PY - 2011/08/17/accepted PY - 2011/11/22/entrez PY - 2011/11/22/pubmed PY - 2012/5/15/medline SP - 395 EP - 402 JF - Journal of physiology and pharmacology : an official journal of the Polish Physiological Society JO - J Physiol Pharmacol VL - 62 IS - 4 N2 - Pharmacological activation of the glucagon-like peptide-1 (GLP-1) receptor and inhibition of the cannabinoid CB1 receptor were found to reduce food intake and body weight in humans and animals. Since earlier studies revealed that endocannabinoids may interact with other neurotransmitters to affect feeding behavior, we have examined whether a stable GLP-1 agonist, exendin-4 and a CB1 receptor antagonist, AM 251, may reciprocally enhance their inhibitory effects on food consumption in the rat. Additionally, we have tested whether the blockade of the GLP-1 receptor by exendin (9-39) modifies AM 251-dependent effects on energy balance. In a dose-response study, male Wistar rats were injected intraperitoneally with either 1.5-6.0 μg/kg exendin-4, 0.5-2 mg/kg AM 251, 80-320 μg/kg exendin (9-39) or their vehicle and the daily food and water intake as well as body weight changes were monitored two days before and two days after the injection. Exendin-4 at a dose of 3.0 and 6.0 μg/kg and AM 251 at a dose 2 mg/kg decreased significantly 24-hour food intake and body weight. Therefore, in the next study, the effects of lower doses of exendin-4 (1.5 μg/kg) and AM 251 (1.0 mg/kg) administered alone or together on food consumption were compared. As opposed to being injected alone, the co-administration of the two resulted in a marked decrease in both daily food intake and body weight. Exendin (9-39) did not modify the suppressory effect of the highest AM 251 dose on food consumption. Apparently, the effect of AM 251 on the appetite is not mediated by GLP-1. The concomitant stimulation of GLP-1 receptor and blockade of CB1 receptor, however, may act synergistically to inhibit appetite in the rat. SN - 1899-1505 UR - https://www.unboundmedicine.com/medline/citation/22100840/Combined_stimulation_of_glucagon_like_peptide_1_receptor_and_inhibition_of_cannabinoid_CB1_receptor_act_synergistically_to_reduce_food_intake_and_body_weight_in_the_rat_ L2 - http://www.jpp.krakow.pl/journal/archive/08_11/pdf/395_08_11_article.pdf DB - PRIME DP - Unbound Medicine ER -