Kainic acid lesions of the parvocellular paraventricular nucleus of the hypothalamus abolish neuropeptide y stimulated gastric activity

Abstract

We have previously shown centrally administered Neuropeptide Y (NPY) to stimulate gastric acid secretion and motility via a vagal pathway. Further, using Fog immunohistochemistry in combination with both intraeerebroventricular (ICV) and micro-injections of NPY in and around the paraventrieular nucleus (PVH), we have proposed the parvocellular (pPVH) region of the PVH to mediate this excitation of gastric function. The purpose of this study was to examine this proposed mechanism with selective lesioning of the pPVH with kainic acid. Male Sprague-Dawley rats were randomly placed into one of four treatment groups: i) untreated, saline injection; 2) untreated, NPY injection; 3) sham-treated, NPY injection; and 4) kainate-treated, NPY injection. Groups 3 and 4 were pre-treated, at least 3 days prior to experimentation, as follows: bilateral injections of either PBS vehicle (100 hi) or kainic acid (0.5-1.0/zg/50-100 nl) were performed with a glass micro-injector inserted into the pPVH. On the day of experimentation, all rats were anaesthetized with urethane, implanted with ICV guide cannulae and set up to continuously monitor gastric acid secretion 0zeq. H ÷) and motility (mmHg). Following stabilization, rats were injected (ICV) with either saline (5 #l) or NPY (200 pM/5 FI). At the end of the experiment, rats were perfnsed with 4% paraformaldehyde and the brains were removed, fixed and sectioned (40 t~m). Sites of kainate lesions were later verified using KluverBarrera staining. Increased acid secretion and motility were observed within 10 + 2 rain following ICV injections of NPY in both untreated and sham-treated groups, which did not significantly differ from one another. Both gastric parameters followed similar time courses by peaking within 30 rain of injection and returning to pre-injection baseline levels within 60-75 rain of injection. Both the untreated saline-injected and the pPVH kainate-treated NPY-injected groups showed no significant enhancement, of either gastric acid secretion or motility. Further, kainate injections located outside of the pPVH did not prevent NPY-induced gastric activity. We conclude that NPY mediates an excitation of gastric acid secretion and motility by acting on neurons of the pPVH. Supported by the Alberta Heritage Foundation for Medical Research and the Medical Research Council of Canada. DOES MUCOSAL ACID EXPOSURE SENSITIZE ESOPHAGEAL MECHANORECEPTORS? P. Peohini, L. Leite, B. Johnston, D. Castell. The Graduate Hospital, Philadelphia, PA. Objective: To assess the effect of acid infusion on the response of normal subjects to both progressive and sustained intraesophageal balloon distention (IEBO). Methods: 21 healthy volunteers; (mean age 36.4 y (21-60); 7 females, 14 males) underwent IEBD using a 30 co latex balloon 0Nilson-Cook, 14 Fr catheter) placed 5 cm above the manometrically located LES. The balloon was progressively inflated at a rate of 1.4 cc/s and subjects were asked to indicate both the first perception of sensation and onset of pain during inflation, volumes being recorded at both points. The balloon was deflated at the point where a subject indicated pain. Maximum inflation volume was limited to 30 cc. This procedure was then repeated. The balloon was then inflated (1.4 cc/s) to a volume 2 cc lower than the minimal volume which provoked sensation, was kept inflated for a maximum of 60 sac and the time to the onset of sensation and pain recorded. A 0.1 N HCI solution was then infused (8cc/min for 15 minutes) proximal to the balloon. Sensory and pain thresholds were then assessed in the same manner following acid infusion. Results: The correlation coefficients between balloon volumes during first and second inflations, both pre and post acid infusion, was highly significant (p < 0.00001) for both sensation (r = 0.75) and pain (r = 0.84), indicating excellent reproducibility of thresholds to IEBD. Following acid infusion, no significant changes were found in threshold volumes or time to reach thresholds, all values shown in table as median Iran~le): SENSATION PAIN PRE-ACID POST-ACID PRE-AClD POST-ACID PROGRESSIVE 24cc 22cc 29cc 27.5cc INFLATION THRESHOLDS (17-29.51 (12-29) I20.5--30) 120-30) PROLONGED INFLATION 9 sec 5 see 57 sec 35 sec {time to {0-60) (3-60) {0-60) (0-60) symptom) With sustained inflation, 19 (90%) of the 21 subiects experienced sensation and 11 (52%) experienced pain at a volume below their previous threshold. Conclusion: t. Sensation and pain thresholds during IEBD are highly reproducible. 2. Chemoreceptor stimulation by acid infusion does not lead to sensitization of mechanoreceptors using either slow balloon distention or sustained balloon inflation in normal subjects.