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GHRP‐6‐Induced Changes in Electrical Activity of Single Cells in the Arcuate, Ventromedial and periventricular nucleusriventricular Nuclei of a Hypothalamic Slice Preparation in Vitro
Author(s) -
A. K. Hewson,
Odile Viltart,
D. N. Mckenzie,
R. E. J. Dyball,
Suzanne L. Dickson
Publication year - 1999
Publication title -
journal of neuroendocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.062
H-Index - 116
eISSN - 1365-2826
pISSN - 0953-8194
DOI - 10.1046/j.1365-2826.1999.00408.x
Subject(s) - arcuate nucleus , medicine , endocrinology , somatostatin , hypothalamus , secretagogue , slice preparation , chemistry , periventricular nucleus , nucleus , growth hormone secretagogue receptor , ghrelin , hormone , biology , receptor , microbiology and biotechnology
Previously, we demonstrated that systemic injection of the growth hormone secretagogue, growth hormone‐releasing peptide (GHRP)‐6, selectively activated cells in the hypothalamic arcuate nucleus, as reflected by increased electrical activity and induction of the immediate early gene c‐ fos . The growth hormone secretagogue receptor distribution is not confined to the arcuate nucleus, suggesting that additional sites of action may exist. In the present study we characterized the electrophysiological responses of cells in the arcuate nucleus, ventromedial nucleus and periventricular nucleus in an in‐vitro hypothalamic slice preparation, following bath application of GHRP‐6. Additionally, since central somatostatin administration has been shown to attenuate the induction of the c‐ fos gene by GHRP‐6, we sought to determine whether the arcuate cells activated by GHRP‐6 are also somatostatin‐sensitive. Male Wistar rats (100–150 g body weight (BW)) were anaesthetized (urethane; 1.2 g/kg BW) and the brains removed. Coronal sections (400 μm thickness) were cut through a block of hypothalamus and were transferred to a slice chamber perfused with artificial cerebrospinal fluid. Forty‐one arcuate nucleus cells were tested with bath application of 15 μm GHRP‐6 for 10 min, 16 of which were tested subsequently (>30 min later) with application of 10 μ M somatostatin. Following GHRP‐6 administration, 19 cells (46.3%) showed a significant increase in firing rate during the 15‐min period after GHRP‐6 application (P<0.001), 17 cells (41.5%) did not respond and the remaining five cells (12.2%) were significantly inhibited. Six of the eight arcuate nucleus cells that were excited by GHRP‐6 were significantly inhibited by somatostatin. By contrast, five of the six arcuate nucleus cells that were unresponsive to GHRP‐6 were also unresponsive to somatostatin. In the ventromedial nucleus, of 19 cells tested, eight cells (42.1%) were excited by GHRP‐6, eight cells (42.1%) were unresponsive and the remaining three cells (15.8%) were significantly inhibited. Of 19 cells recorded in the periventricular nucleus, 13 (68.4%) were unresponsive to GHRP‐6 and six (31.6%) were significantly inhibited. Thus, electrophysiological studies in vitro suggest that: (1) neurones in the hypothalamic arcuate nucleus, ventromedial nucleus and periventricular nucleus show changes in electrical activity in response to GHRP‐6; and (2) the arcuate nucleus cells excited by GHRP‐6 are also subject to inhibitory control by somatostatin.