Exp Clin Endocrinol Diabetes 1994; 102(2): 111-117
DOI: 10.1055/s-0029-1211272
Original

© J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart · New York

In vivo-effect of intraadrenal nicotine and substance P application on rat adrenal medullary catecholamine secretion

J.-P. Voigt, G. Kaufmann, B. Hirsch, S. Leonhardt, H. Jarry, P. Oehme** , W. Wuttke***
  • University of Göttingen, Division of Clinical and Experimental Endocrinology, Department of Obstetrics and Gynecology, Göttingen, Germany
** Institute of Molecular Pharmacology, Alfred-Kowalke-Str. 4, D-10315 Berlin, FRG *** To whom all correspondence should be addressed: Prof. Dr. W. Wuttke, Abteilung für Klinische und Experimentelle Endokrinologie, Universitäts-Frauenklinik, Robert-Koch-Straße 40, D-37075 Göttingen, Germany
Further Information

Publication History

Publication Date:
15 July 2009 (online)

Summary

The present study was conducted to characterize in vivo the intraadrenal catecholamine (CA) secretion in rats. This was possible by using a microdialysis System (MDS) which mimics some properties of an artificial capillary One end of this System was connected to a peristaltic pump, from the other end fractions were sampled at 5 min intervals. Concentrations of epinephrine (E) and norepinephrine (NE) in adrenal dialysate fractions were determined by HPLC electrochemical detection. Through this MDS nicotine was administered directly into the adrenal medulla of freely moving rats and the response of catecholamine release was determined. In the second part of the study the effect of exogenous substance P (SP) on spontaneous as well as on nicotine-stimulated CA release was investigated. Like nicotine, SP was administered directly into the adrenal medulla. At a flow rate of 25 ul/min the transfer rates of CA and nicotine were approximately 1% whereas SP passed at a rate of 01.–0.2%.

Under resting conditions CA release remained constant. In response to 2 × 10−7 M nicotine (which resulted in local concentration of 2 × l0−7 M), E and NE secretion increased 2.9 and 5.4-fold, respectively However, due to an increased E response this difference attenuated with a later onset of the first Stimulus. The higher concentrations of 10−4 M resulted in 8.1 and 10.8-fold increases for E and NE. This latter response is clearly supraphysiologic and therefore the 2 × 10−5 M concentration was used for further experimentation. CA secretion was stimulated with nicotine four times at 30 min intervals. The amplitude of NE secretion in response to nicotine declined from the first to the last stimulus indicating de-sensitization of the response. No such desensitization was observed for the E response.

At local concentrations of 10−8 M (i. e. concentrations in the MDS = 10−5 M) SP did not affect basal NE secretion, when administered one hour before the first of four stimulations with nicotine. In contrast, SP provoked a significant elevation of E secretion and this effect was additive to the nicotine-induced effect. After SP, no significant desensitization of the nicotinic NE response was observed.

This is the first time that in freely moving rats a desensitization of the secretory response of NE after intraadrenal nicotine administration was demonstrated. The results give further evidence for an involvement of SP in the regulation of intraadrenal CA release, probably by different effects on E and NE release.

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