Endocrinology, Vol 127, 1646-1655, Copyright © 1990 by Endocrine Society

ARTICLES

Catecholamines mediate nicotine-induced adrenocorticotropin secretion via alpha-adrenergic receptors

SG Matta, J Singh and BM Sharp
Endocrine Neuroscience Laboratories, Minneapolis Medical Research Foundation, Minnesota.

Previous studies determined that iv nicotine stimulates ACTH secretion by acting on sites accessible from the fourth ventricle (IV), rather than directly on CRF-containing neurons in the hypothalamus. Brainstem catecholaminergic cell groups, which are accessible from the IV, project to the hypothalamus and stimulate the secretion of CRF and ACTH. Therefore, these studies investigated the role of catecholamines in nicotine-stimulated ACTH secretion. Experiments with the catecholaminergic neurotoxin, 6-hydroxydopamine, demonstrate that the ACTH response to nicotine delivered iv (0.03 or 0.05 mg/kg body wt) or instilled into the IV (1 or 2.5 micrograms) was significantly reduced in lesioned animals (P less than 0.01). Selective inhibitors of epinephrine synthesis, SKF 64139 and 2,3-dichloro-alpha- methylbenzylamine (DCMB), significantly reduced (P less than 0.01) the ACTH response to 0.05 mg/kg body wt nicotine iv, without affecting median eminence CRF content. Because controversy exists about the effect of DCMB as an alpha 2 adrenoreceptor antagonist in vivo, this was examined by administering norepinephrine into the third ventricle after DCMB ip; DCMB significantly reduced the ACTH response to norepinephrine 0.2 micrograms (P less than 0.05) but not to 0.5 micrograms. To determine whether alpha 2 receptors are indeed involved in the ACTH response to nicotine, yohimbine, an alpha 2 antagonist, was injected into the third ventricle before nicotine injection into the IV. Yohimbine significantly reduced the ACTH response. Thus, the secretion of both hypothalamic epinephrine and, to some extent, norepinephrine is involved in the ACTH response to the activation of catecholaminergic neurons in the IV. Further investigation of the adrenergic receptor(s) involved compared the ACTH response to nicotine (1 microgram) instilled into the IV after prazocin (alpha 1 antagonist), or propranolol (beta antagonist) was injected into the third ventricle. Prazocin significantly reduced (P less than 0.05) the ACTH response, whereas propranolol was ineffective. Thus, both alpha 1 and alpha 2 receptors are involved in mediating the ACTH response to nicotine.

This article has been cited by other articles:

				R. Zhao, H. Chen, and B. M. Sharp Nicotine-Induced Norepinephrine Release in Hypothalamic Paraventricular Nucleus and Amygdala Is Mediated by N-Methyl-D-aspartate Receptors and Nitric Oxide in the Nucleus Tractus Solitarius J. Pharmacol. Exp. Ther., February 1, 2007; 320(2): 837 - 844. [Abstract] [Full Text] [PDF]

				A. M. Rasmusson, M. R. Picciotto, and S. Krishnan-Sarin Smoking as a complex but critical covariate in neurobiological studies of posttraumatic stress disorders: a review J Psychopharmacol, September 1, 2006; 20(5): 693 - 707. [Abstract] [PDF]

				M. E. Myles, A. M. Azcuy, N. T. Nguyen, E. R. Reisch, S. A. Barker, H. W. Thompson, and J. M. Hill Bupropion (Zyban, Wellbutrin) Inhibits Nicotine-Induced Viral Reactivation in Herpes Simplex Virus Type 1 Latent Rabbits J. Pharmacol. Exp. Ther., November 1, 2004; 311(2): 640 - 644. [Abstract] [Full Text] [PDF]

				Y. Fu, S. G. Matta, V. G. Brower, and B. M. Sharp Norepinephrine Secretion in the Hypothalamic Paraventricular Nucleus of Rats during Unlimited Access to Self-Administered Nicotine: An In Vivo Microdialysis Study J. Neurosci., November 15, 2001; 21(22): 8979 - 8989. [Abstract] [Full Text] [PDF]

				D.-K. SONG, Y.-B. IM, J.-S. JUNG, H.-W. SUH, S.-O. HUH, J.-H. SONG, and Y.-H. KIM Central injection of nicotine increases hepatic and splenic interleukin 6 (IL-6) mRNA expression and plasma IL-6 levels in mice: involvement of the peripheral sympathetic nervous system FASEB J, July 1, 1999; 13(10): 1259 - 1267. [Abstract] [Full Text]

				C. W. Wuenschell, J. Zhao, J. D. Tefft, and D. Warburton Nicotine stimulates branching and expression of SP-A and SP-C mRNAs in embryonic mouse lung culture Am J Physiol Lung Cell Mol Physiol, January 1, 1998; 274(1): L165 - L170. [Abstract] [Full Text] [PDF]

				Y. Fu, S. G. Matta, J. D. Valentine, and B. M. Sharp Adrenocorticotropin Response and Nicotine-Induced Norepinephrine Secretion in the Rat Paraventricular Nucleus Are Mediated through Brainstem Receptors Endocrinology, May 1, 1997; 138(5): 1935 - 1943. [Abstract] [Full Text] [PDF]