Nature 319, 147 - 150 (09 January 1986); doi:10.1038/319147a0

Functional corticotropin releasing factor receptors in the primate peripheral sympathetic nervous system

Robert Udelsman^*, James P. Harwood, Monica A. Millan, George P. Chrousos^†, David S. Goldstein^‡, Reuven Zimlichman^‡, Kevin J. Catt & Greti Aguilera

Endocrinology and Reproduction Research Branch, NICHD; ^*Surgery Branch, NCI; ^†Developmental Endocrinology Branch, NICHD; and ^‡Hypertension-Endocrine Branch, NHLBI, National Institutes of Health, Bethesda, Maryland 20892, USA

Corticotropin releasing factor (CRF) is a key hormone in the integrated response to stress, acting both as the major regulator of pituitary adrenocorticotropic hormone (ACTH) release and as a neuropeptide in the brain^1,2. The actions of CRF are mediated by specific plasma membrane receptors in the anterior pituitary gland³ and in discrete brain areas including the cerebral cortex and several regions related to the limbic system^4,5. In addition to the pituitary and central actions of CRF, systemic administration of the peptide in the rat⁶, dog^7,8, monkey⁹ and man¹⁰⁻¹² causes hypotension and tachycardia because of a decrease in peripheral vascular resistance. These observations, in conjunction with the finding of immunoreactive¹³⁻¹⁷ and bioactive^14,18 CRF in peripheral tissues, suggest that the peptide is locally released in tissues to act as a neurotransmitter or paracrine hormone. As CRF is present in the adrenal medulla^13,14 and the peptide is known to modulate the central activity of the autonomie nervous system¹, we investigated the possibility that CRF is involved in the regulation of the peripheral autonomie nervous system. Such an action of CRF is supported by our demonstration of specific CRF receptors in the monkey adrenal medulla and sympathetic ganglia. In the adrenal medulla, these receptors are coupled to adenylate cyclase and can stimulate the secretion of catecholamines and Met-enkephalin.

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