The ternary complex model suggests that G-protein-coupled receptors resonate between inactive (R) and active (R*) forms. Physiologically, R sites ordinarily predominate with a few R* sites giving rise to basal activity. Agonists recognize, stabilize and increase the R* population, thus altering intracellular activity. There is evidence to suggest the possibility of a spectrum of conformations b...

Glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) are potent insulinotropic peptides released from the small intestine. To examine their relative contribution to postprandial insulin release, a specific GIP antagonist (ANTGIP) and a GLP-1 antagonist, exendin-(9-39)-NH2, were infused into rats after an intragastric glucose meal. In control rats, plasma glucos...

In the present study, the effects of excitation and inhibition of GABAA and GABAB receptor subtypes on the expression of morphine-induced conditioned place preference (CPP) were investigated. For this purpose, male Wistar rats (250-300 g) were used in the experiments. Five days after surgical cannulation in the ventral tegmental area (VTA), different doses of morphine were injected into the ani...

Glucagon stimulates hepatic glucose production by activating specific glucagon receptors in the liver, which in turn increase hepatic glycogenolysis as well as gluconeogenesis and ureagenesis from amino acids. Conversely, glucagon secretion is regulated by concentrations of glucose and amino acids. Disruption of glucagon signaling in rodents results in grossly elevated circulating glucagon leve...

It has been reported that ketamine as an uncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist has also non-NMDA receptor antagonist properties. We recently found that ketamine (20 ?M) affected differently induction of NMDA receptor-mediated long-term potentiation (LTP) when administered 30 min prior to tetanic Primed-Bursts (PBs) stimulation. On the other hand, ketamine also influenced...

To find mammalian analogues of exendin-4, a peptide from Helodermatidae venoms that interacts with newly discovered exendin receptors on dispersed acini from guinea pig pancreas, we examined the actions of recent additions to the vasoactive intestinal peptide/secretin/glucagon family of regulatory peptides. In every respect tested, the truncated form of glucagon-like peptide-1, GLP-1(7-36)NH2, ...

The glucagon-like peptide (GLP)-1 receptor is a promising target for the treatment of type 2 diabetes and obesity, and there is great interest in characterizing the pharmacology of the GLP-1 receptor and its ligands. In the present report, we have applied bioluminescence resonance energy transfer assays to measure agonist-induced recruitment of betaarrestins and G-protein-coupled receptor kinas...

Infants with congenital hyperinsulinism owing to inactivating mutations in the K(ATP) channel (K(ATP)HI) who are unresponsive to medical therapy will require pancreatectomy to control the hypoglycemia. In preclinical studies, we showed that the GLP-1 receptor antagonist exendin-(9-39) suppresses insulin secretion and corrects fasting hypoglycemia in SUR-1(-/-) mice. The aim of this study was to...

Charbonneau, Alexandre, Alexandre Melancon, Carole Lavoie, and Jean-Marc Lavoie. Alterations in hepatic glucagon receptor density and in Gs and Gi 2 protein content with diet-induced hepatic steatosis: effects of acute exercise. Am J Physiol Endocrinol Metab 289: E8–E14, 2005. First published February 1, 2005; doi:10.1152/ajpendo.00570.2004.—The present study was undertaken to test the hypothes...

In order to clarify the potential roles of glucagon for energy induction during the perinatal period, the developmental changes of serum glucagon concentration, the ontogenesis of hepatic glucagon receptor and glucagon-sensitive adenylate cyclase system were estimated in comparison with insulin in rats. In fetal rats on day 18 to 20 gestation, serum glucose levels and hepatic glycogen contents ...