IN-VIVO EFFECT OF INTRAADRENAL NICOTINE AND SUBSTANCE-P APPLICATION ON RAT ADRENAL-MEDULLARY CATECHOLAMINE SECRETION

The present study was conducted to characterize in vivo the intraadren al catecholamine (CA) secretion in rats. This was possible by using a microdialysis system (MDS) which mimics some properties of an artifici al capillary One end of this system was connected to a peristaltic pum p, from the other end fractions were sampled at 5 min intervals. Conce ntrations of epineph rine (E) and norepinephrine (NE) in adrenal dialy sate fractions were determined by HPLC electrochemical detection. Thro ugh this MDS nicotine was administered directly into the adrenal medul la of freely moving rats and the response of catecholamine release was determined. In the second part of the study the effect of exogenous s ubstance P (SP) on spontaneous as well as on nicotine-stimulated CA re lease was investigated. Like nicotine, SP was administered directly in to the adrenal medulla. At a now rate of 25 mu l/min the transfer rate s of CA and nicotine were approximately 1% whereas SP passed at a rate of 01.-0.2%. Under resting conditions CA release remained constant. I n response to 2x10(-7) M nicotine (which resulted in local concentrati on of 2x10(-7) M), E and NE secretion increased 2.9 and 5.4-fold, resp ectively. However, due to an increased E response this difference atte nuated with a later onset of the first stimulus. The higher concentrat ions 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 2x 10(-5) M concentration was used for further experimentation. CA secret ion was stimulated with nicotine four times at 30 min intervals. The a mplitude of NE secretion in response to nicotine declined from the fir st to the last stimulus indicating desensitization of the response. No such desensitization was observed for the E response. At local concen trations of 10(-8) M (i. e. concentrations in the MDS = 10(-5) M) SP d id not affect basal NE secretion, when administered one hour before th e 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 re sults give further evidence for an involvement of SP in the regulation of intraadrenal CA release, probably by different effects on E and NE release.