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

Abstract

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 brain1,2. 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 system4,5. In addition to the pituitary and central actions of CRF, systemic administration of the peptide in the rat6, dog7,8, 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 bioactive14,18 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 medulla13,14 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.