Neuropeptide Y augments adrenergic contractions at feline lower esophageal sphincter

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Abstract
The purpose of this study was to determine the anatomic and physiological interactions between neuropeptide Y (NPY) and adrenergic transmitters at the feline lower esophageal sphincter (LES). Intraluminal pressures of the esophagus, LES, and gastric fundus were recorded in anesthetized cats. In a separate group of cats, gastroesophageal junctions were removed after locating the LES manometrically. Adjacent sections were stained with antibodies for NPY and tryosine hydroxylase (TH). Indirect immunofluorescence revealed staining of TH- and NPY-like immunoreactive (LI) nerves in the circular muscle of the LES. Staining was also present for NPY-LI in the longitudinal muscle, muscularis mucosa, periarterial nerves, and nerves and cell bodies of the myenteric plexus of the LES. In vivo, NPY produced a biphasic effect at the LES with an initial contraction (lasting .apprx. 30 s) followed by a relaxation (lasting .apprx. 3 min). NPY at the dose giving 50% of the maximum response (10-6 g/kg) induced a contraction of 14.8 .+-. 5.0 mmHg (P < 0.05) followed by a decrease of basal LES pressure from 29.2 .+-. 4.7 to 19.4 .+-. 2.9 mmHg (P < 0.01). Propranolol and phentolamine had no influence on either effect of NPY. Tetrodotoxin and atropine antagonized the LES contraction to the maximal effective dose of NPY (10-5 g/kg) by 83.3 .+-. 4.5% (P < 0.01) and 84.5.+-. 7.9% (P < 0.01), respectively. NPY at the threshold dose (10-7 g/kg) augmented the peak contraction to a submaximal dose of phenylephrine (10-6 g/kg) from 29.0 .+-. 4.8 to 62.3 .+-. 8.4 which was not antagonzied by atropine (68.4 .+-. 15.9 mm Hg) or tetrodotoxin (70.8 .+-. 6.9 mmHg). These studies suggest that 1) there is a dense innervation of the feline LES by both NPY- and TH-LI nerves, 2) NPY has a biphasic response at the feline LES, in vivo, with an initial cholinergically mediated contraction, and 3) NPY augments the LES response to phenylephrine by a noncholinergic mechanism. Thus NPY shows both structural and functional interrelationships with adrenergic neurons at the feline lower esophageal sphincter.