Angiotensin behaves like a paracrine mediator in guinea pig enteric nervous system (874.1)

Abstract

Enteric mast cell hyperplasia occurs in inflammatory bowel disease and the irritable bowel syndrome. Mast cell proteases are catalysts for conversion of angiotensin I to angiotensin II (AT‐II). We applied AT‐II to ENS neurons, while recording neuronal electrical and synaptic behavior. The AT‐II acted to elevate or suppress neuronal excitability. Suppression of was reversed by noradrenergic alpha2 receptor blocking drugs. AT‐II enhanced electrically‐evoked noradrenergic inhibitory postsynaptic potentials and suppressed fast and slow excitatory postsynaptic potentials. Selective AT‐II1 receptor blocking drugs, but not selective AT2 receptor antagonists, suppressed all actions of AT‐II. AT2 receptor protein and the AT2 mRNA transcript were expressed in the ENS. The AT1 receptor was not expressed. Immunoreactivity for the AT1 receptor was expressed by ENS neurons with AH‐type 2 and S‐type electrophysiological behavior. Our results predict that mast cell‐induced AT‐II formation will have paracrine function in the ENS that includes enhanced release of norepinephrine from sympathetic postganglionic axons. Elevation of norepinephrine represses excitatory neurotransmission in the neural networks of the brain‐in‐the‐gut and suppresses neurogenic secretion thru inhibition of excitability of secretomotor neurons in the submucosal division of the ENS.Grant Funding Source: Supported by National Institutes of Health, R01DK037238