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Release of Corticotropin-Releasing Factor from Rat Brain Regions in Vitro^*

MARK A. SMITH, GARTH BISSETTE, THEODORE A. SLOTKIN, DAVID L. KNIGHT and CHARLES B. NEMEROFF

Departments of Psychiatry and Pharmacology and the Center for Aging and Human Development, Duke University Medical Center Durham, North Carolina 27710

Address requests for reprints to: Dr. Charles B. Nemeroff, Laboratory of Psychoneuroendocrinology, Duke University, Box 3859, Durham, North Carolina 27710.

Abstract

In addition to its endocrine action in the anterior pituitary, corticotropin-releasing factor (CRF) also appears to play a role in regulating higher central nervous system function(s). To investigate further the role of CRF in brain, a specific RIA was used to measure in vitro CRF release during incubation of various rat brain regions in Krebs-Henseleit buffer. Increasing the potassium concentration to 56 mM resulted in a 10-fold increase in CRF release from minced hypothalamus. However, the high K⁺ concentrations had no effect in the presence of calcium-free buffer containing 1 mM EGTA. Scorpion venom also stimulated CRF release in a calcium-dependent manner. CRF-like immunoreactivity was detected in extrahypothalamic brain regions using RIA and HPLC. Significant calciumdependent CRF release from the rat amygdala and midbrain was observed in response to 56 mM K⁺ or scorpion venom. These results indicate that depolarizing agents induce the release of CRF-like immunoreactivity not only from the hypothalamus but also from other rat brain regions and lend further support to the hypothesis that CRF may be a neurotransmitter or neuromodulator in the central nervous system. (Endocrinology 118: 1997–2001, 1986)

Footnotes

^* This work was supported by NIMH Grants MH-39415 and MH- 40524 and the Gorrell Family Psychiatric Research Fund.

Recipient of a Nanaline Duke Scholarship.

Received September 4, 1985.

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