Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:4.6.1.1 (adenylate cyclase)
 19,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The pancreatic gland has an enormous potential for growth and regeneration, mainly in rodents. These processes remain mostly under the control of the GI hormone cholecystokinin (CCK). The human pancreas however does not show proliferative properties after partial pancreatectomy, but research in this field has been scarce. Recent studies indicate that CCK might not be the expected trophic agent since its two receptors CCK(A) and CCK(B) were not found on human exocrine pancreas. Therefore, if human pancreas grows and regenerates, it has to be under the influence of some unknown trophic factors. Neuropeptides receiving much attention lately as regulators of pancreatic functions could be among the searched trophic agents. This presentation focus on neuropeptides growth potential: GRP-Bombesin, GABA, PP, PYY, Neurotensin, SP, VIP, PACAP, CGRP and galanin. Some neuropeptides have moderate effects on pancreatic enzymes and electrolytes secretion: SP, VIP, PACAP. However, their trophic effects remain unexplored except for GRP-bombesin and PACAP. PACAP preferentially exhibits its mitogenic and proliferative effects on the pancreatic acinar cells AR4-2J via tyrosine kinase, phospholipase D and ornithine decarboxylase activation but not through adenylate cyclase. The growth promoting action of GRP-bombesin is well documented on rodent's pancreas. However, recent studies indicate that this neuropeptide is potentially trophic for larger mammals' pancreas. Indeed, investigators recently documented that bombesin induced pancreatic regeneration in the pig after partial pancreatectomy through mitogen-activated protein kinases activation as do CCK-8 and caerulein on rat pancreas. Have we found the magic pancreatic trophic factor in large mammals? Further investigations will tell.
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PMID:Intervention of GI neuropeptides in pancreatic growth and regeneration: comparison with cholecystokinin. 1507 55

Neuropeptide Y (NPY) was first reported as an abundant peptide in brain tissue in 1982. Shortly thereafter, NPY was found to be a member of a peptide family consisting of the endocrine peptides pancreatic polypeptide (PP) and peptide YY (PYY). These peptides exert most of their biological effects through five G-protein coupled receptors termed Y1, Y2, Y4, Y5 and y6 that mediate either inhibition adenylate cyclase or increases in intracellular calcium. Since the discovery of NPY, a robust a body of literature has developed around the potential functions of this peptide. While initial findings identified NPY is an important contributor to the regulation of feeding, body weight and blood pressure, more recent work as revealed more subtle functions of this peptide and its potential role in affective disorders, bone formation and cravings. The accompanying twelve reviews detail important developments in our understanding of the functional role of NPY.
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PMID:Introduction to the reviews on neuropeptide Y. 1533 66

The neurohormonal control of pancreatic exocrine secretion is a complex interaction of multiple pathways involving a large number of gut hormones, neurotransmitters, and neuropeptides. Recent studies have elucidated a role for cholecystokinin in the regulation of bicarbonate and fluid secretion from pancreatic duct cells and suggested that cholecystokinin stimulation of human pancreatic acinar cells is likely regulated by an indirect mechanism of stimulation of afferent neurons. Evidence supports the regulation of potassium channels in rat pancreatic acinar cells by the cyclic AMP-mediated agonist secretin. Mechanisms for the regulation of cholecystokinin and secretin release by releasing factors have also been elucidated. The area postrema has been implicated in the mediation of inhibition of pancreatic secretion by the gut hormones peptide YY and pancreatic polypeptide. The neurotransmitter serotonin has been demonstrated to play a role in acid-induced secretin release and in pancreatic secretion stimulated by luminal factors. The regulation of pancreatic exocrine secretion by purines, nitric oxide, and gamma-aminobutyric acid as well as by the neuropeptides pituitary adenylate cyclase-activating peptide, gastrin-releasing peptide, and substance P is reviewed. The role of the central nervous system in modulating pancreatic secretion is also described. This review highlights the recent advances in knowledge of the neurohormonal regulation of pancreatic exocrine secretion.
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PMID:Neurohormonal control of pancreatic exocrine secretion. 1703 30

Pituitary adenylate cyclase-activating peptide (PACAP) is expressed within the gastroenteric system, where it has profound physiological effects. PACAP was shown to regulate food intake and thermogenesis centrally; however, PACAP peripheral regulation of appetite and feeding behavior is unknown. Therefore, we studied PACAP's effect on appetite and food intake control by analyzing feeding behavior and metabolic hormones in PAC1-deficient (PAC1-/-) and age-matched wild-type (WT) mice intraperitoneally injected with PACAP1-38 or PACAP1-27 before the dark phase of feeding. Food intake and feeding behavior were analyzed using the BioDAQ system. Active ghrelin, glucagon-like peptide-1 (GLP-1), leptin, peptide YY, pancreatic polypeptide, and insulin were measured following PACAP1-38 administration in fasted WT mice. PACAP1-38/PACAP1-27 injected into WT mice significantly decreased in a dose-dependent manner cumulative food intake and reduced bout and meal feeding parameters. Conversely, PACAP1-38 injected into PAC1-/- mice failed to significantly change food intake. Importantly, PACAP1-38 reduced plasma levels of active ghrelin compared with vehicle in WT mice. In PAC1-/- mice, fasting levels of active ghrelin, GLP-1, insulin, and leptin and postprandial levels of active ghrelin and insulin were significantly altered compared with levels in WT mice. Therefore, PAC1 is a novel regulator of appetite/satiety. PACAP1-38/PACAP1-27 significantly reduced appetite and food intake through PAC1. In PAC1-/- mice, the regulation of anorexigenic/orexigenic hormones was abolished, whereas active ghrelin remained elevated even postprandially. PACAP significantly reduced active ghrelin in fasting conditions. These results establish a role for PACAP via PAC1 in the peripheral regulation of appetite/satiety and suggest future studies to explore a therapeutic use of PACAP or PAC1 agonists for obesity treatment.
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PMID:PACAP intraperitoneal treatment suppresses appetite and food intake via PAC1 receptor in mice by inhibiting ghrelin and increasing GLP-1 and leptin. 2633 28


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