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Intracerebroventricular and intravenous administration of growth hormone secretagogue L-692,585, somatostatin,neuropeptide Y and galanin in pig: Dose-dependent effects on growth hormone secretion
Authors:S-J Cho  J-S Lee  ED Mathias  C Chang  GJ Hickey  S Lkhagvadorj  LL Anderson
Institution:1. Department of Animal Science, Iowa State University, Ames, IA 50011, USA;2. Department of Biomedical Sciences, Iowa State University, Ames, IA 50011, USA;3. Interdepartmental Neuroscience Program, Iowa State University, Ames, IA 50011, USA;4. Department of Pharmacology, Merck Research Laboratories, Rahway, NJ 07065, USA;1. Department of Physiology, Medical College of Qingdao University, Qingdao, Shandong 266071, China;2. Department of Internal Medicine, Medical College Affiliated General Hospital, Qingdao, Shandong 266021, China;3. Department of Anesthesiology, Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095, USA;1. Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea;2. Greencross Research Institute, Yongin, Kyeonggi-Do, Korea;1. Keldysh Institute of Applied Mathematics of RAS, Russian Federation;2. Moscow Institute of Physics and Technology, Russian Federation;1. Division of Neuroscience, Department of Pharmacology, Shrimati Kishoritai Bhoyar College of Pharmacy, New Kamptee, Nagpur (M.S.) 441002, India;2. Department of Pharmaceutical Sciences, Rashtrasant Tukadoji Maharaj Nagpur University, Nagpur 440033, India;1. Department of Pharmacology, Centro de Investigación Biomédica (CIBM), University of Granada, Spain;2. Department of Psychobiology, Mind, Brain, and Behavior Research Center (CIMCYC), University of Granada, Spain
Abstract:Central regulation of growth hormone (GH) secretion by the GH secretagogue, L-692,585 (585), was determined in Yorkshire barrows (40–45 kg BW) with intracerebroventricular (icv) stainless steel cannulas placed by stereotaxic coordinates and indwelling external jugular vein (iv) cannulas for injecting 585 or saline during 3 h serial blood sampling. Dose-dependent effects of 585 were determined by icv injections of saline vehicle, 3, 10, and 30 μg/kg BW by once daily increment. A switchback study of iv and icv 585 treatment determined central and peripheral regulation of GH secretion by the secretagogue at 30 μg/kg BW. When administered icv, 585 increased GH concentration in a dose-dependent manner, with a return to baseline by 60 min. GH secretion was attenuated by increased numbers of icv 585 injections (p < 0.05); however, it was not affected by increased numbers of iv 585 injections. Icv administration of somatostatin (SRIF) decreased (p < 0.05) GH secretion compared with saline-treated controls, and decreased (p < 0.05) peak GH response when given in combination with 585 as compared with 585 alone. Porcine galanin (pGAL) modestly increased (p < 0.05) GH levels compared with saline controls, but when given icv in combination with 585 peak GH response was lower (p < 0.05) compared with 585 alone. Porcine neuropeptide Y (pNPY) administered icv was without effect on GH levels compared with saline controls and decreased (p < 0.05) peak GH response when given in combination with 585 as compared with 585 alone. The pharmacological actions by icv administration indicate that the GH secretagogue and neuropeptides act at the level of both porcine pituitary and hypothalamus.
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