| IntroductionBombesin (BN ) is a tetradecapeptide which was isolated from an-uran skin in 1970s. Bombesin - like peptides which were similar to BN in many respects ,such as,structure,biological characteristic, physiological role,etc. have been reported to be found in mammalian intestine and brain. They have many physiological role. In this study ,the mechanism underlying thermoregulatory action of bombesin is to be further elucidated.When given intracerebrally bombesin produces hypothermia in many animals, such as, rats, mice, rabbits, etc. Moreover,bombesin can prevent the hyperthermia produced by TRF and PGE2 in rats kept at room temperature. Interferon - a, one of endogenous pyrogens, given intracerebrally, caused a dose - dependent fever. It has been reported that two processes may mediate the pyrogenic effects of a -IFN, viz, an endogenous opioid - and a PGE - dependent mechanism. It is possible that bombesin blocks the changes induced by a -IFN.Now, there is evidence that arginine vasopressin( AVP) acts as a neurotransmitter in the ventral septal area(VSA) where is the most susceptible and first site of action. Intracerebroventricular injection ofBN increased AVP level in the PVN, and neurofibrae of AVP in VSA primarily come from paraventricular nucleus, superaoptic nucleus and bed nucleus of stria terminalis. It is possible that central thermoregu-latory action of BN involves the increase of AVP in the VSA. The aim of the present study was to test that hypothesis by investigating the effects of centrally administered BN on IFN - induced febrile response and AVP level in the brain.Materials and Methods1. Animals and body temperature response measurementAdult male Wistar rats (180 -220g, obtained from the Experimental Animal Center, Chinese Medical University. ) were used in this study . Animals were caged individually and had free access to food and water. The ambient temperature of the animal room was (22 + 2)C; light and darkness were alternated; with light on from 6:00 to 18:00. During experiments each rat was placed individually in a plastic cage without restraint. Rectal temperature was monitored by insertion of a thermister probe 6cm in the rectum, the thermistor was fed into digital thermometer ( SN2202 Type, Beijing Sinan Instruments Factory). Temperature records were taken at 30 min intervals until the experiment was over. All experimental trials were carried out between 7:00 and 14;00.2. Surgical Procedures and administration of test substances Under Ketamin hydrochloride and acepromazine meleate injectionanesthesia ,a guide cannula was inserted into one of the lateral ventricles as described in atlas writen by Louis J. Pellegrine. The animals were allowed to recover for at least 6 days before expermentation. Po-sitioning of cannula was verified histologically at the end of the experiment . Recombinant human interferon a2b ( obtained from ANHUI ANKE Biotechnology co. Ltd) , BN (purchased from Sigma Chemicals Ltd) were injected with the similar velocity.3. Determination of AVP contentThe rats was decapitated at the end of the experiments, then the brain was removed quickly and boiled in normal saline for 5 min. The VSA and hypothalamus were dissected for AVP assay. The concentration of AVP in the VSA or hypothalamus was determined by radioim-munoassay as described earilier using AVP assay kits ( obtained from the Second Military University,Shanghai, China).Results1. The rectal temperature response to intracerebroventricular injection of BN or a - IFN of different doses.Injection (i. c. v. ) of a - IFN caused a dose - dependent fever in rats( P < 0.05); Injection (i. c. v. ) of BN induced a dose - dependent hypothermia( P < 0.01).2. Effect of injection (i. c. v. ) of BN on AVP content hi the VSA and hypothlamus.Introcerebroventricular administration of BN ( 0. 5ug , 5ul ) caused a significant increase in AVP levels of the VSA ( P < 0.05 ) and had no significant changes in AVP levels of the hypothalamus compared with control group ( P > 0. |
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