ABSTRACT
Title
Cholinergic control of peripheral organ dysfunction.
Authors
D. Altavilla1, A. Bitto1, L. Minutoli1, N. Irrera1, S. Guarini2, F. Squadrito1
1Department of Clinical and Experimental Medicine and Pharmacology, University of Messina, Italy.
2Department of Biomedical Sciences, Section of Pharmacology, University of Modena and Reggio Emilia, Modena, Italy.
1Department of Clinical and Experimental Medicine and Pharmacology, University of Messina, Italy.
2Department of Biomedical Sciences, Section of Pharmacology, University of Modena and Reggio Emilia, Modena, Italy.
Abstract
The nervous system, through the vagus nerve, controls inflammation by decreasing the release of tumor necrosis factor-alpha from endotoxin stimulated macrophages. This anti-inflammatory effect is mediated by an interaction of acetylcholine, the principal neurotransmitter of the vagus nerve, with macrophage cholinergic nicotinic receptors expressing the alpha7 subunit. The cholinergic anti-inflammatory pathway inhibits inflammation by suppressing cytokine synthesis via release of acetylcholine in organs of the reticuloendothelial system, including the lungs, spleen, liver, kidneys and gastrointestinal tract.
Acute pancreatitis is an inflammatory condition that may lead to multisystemic organ failure. Melanocortin peptides have been successfully used in experimental models of organ failure and shock, and their protective effect occurs through the activation of a vagus nerve-mediated cholinergic anti-inflammatory pathway by acting at brain melanocortin 4 receptors. In light of these observations, the effects of melanocortin 4 receptor agonist RO27-3225 have been studied in an experimental model of cerulein-induced pancreatitis. Our data show that melanocortin 4 receptor agonists reduce pancreatitis severity through the activation of the cholinergic anti-inflammatory pathway.
Acute pancreatitis is an inflammatory condition that may lead to multisystemic organ failure. Melanocortin peptides have been successfully used in experimental models of organ failure and shock, and their protective effect occurs through the activation of a vagus nerve-mediated cholinergic anti-inflammatory pathway by acting at brain melanocortin 4 receptors. In light of these observations, the effects of melanocortin 4 receptor agonist RO27-3225 have been studied in an experimental model of cerulein-induced pancreatitis. Our data show that melanocortin 4 receptor agonists reduce pancreatitis severity through the activation of the cholinergic anti-inflammatory pathway.