EFFECTS OF CLONIDINE, DIHYDRALAZINE AND SPLANCHNIC NERVE-STIMULATION ON THE RELEASE OF NEUROPEPTIDE-Y, MET-ENKEPHALIN AND CATECHOLAMINES FROM DOG ADRENAL-MEDULLA

Various neuropeptides are costored together with catecholamines in the adrenal medulla. The concurrent release (evaluated by adrenal vein pl asma levels) of these neuropeptides [neuropeptide Y (NPY), met-enkepha line (ME)] and catecholamines [adrenaline (A) and noradrenaline (NA)] from the adrenal gland was examined in chloralose-anesthetized dogs af ter intravenous administration of clonidine (10 mug/kg) and dihydralaz ine (1 mg/kg). These results were compared to those obtained after the stimulation of the right splanchnic nerve at 1, 5 and 10 Hz frequenci es. The increment in the release of catecholamines and neuropeptides w as evaluated for dihydralazine and splanchnic nerve stimulation. Dihyd ralazine (at its maximal effect) induced a significant preferential in crease in catecholamines (expressed as mean (SEM): NA: 17.3 (5.4) fold , A: 13.1 (2.6) fold) and ME (16.0 (7.1) fold) versus basal values. Ho wever, the significant increase in NPY-LI was only 2.0 (0.4) times the baseline. Splanchnic nerve stimulation induced a frequency-dependent increase in catecholamines and neuropeptides. When the stimulation fre quency was increased from 1 Hz to 5 Hz, NA and A levels increased 17.9 (4.3) and 14.0 (2.2) fold, respectively and ME levels 14.1 (3.0) fold . By contrast, NPY-LI was increased only 2.3 (0.3) fold under the same conditions. Increasing the stimulation frequency from 5 Hz to 10 Hz r esulted in similar elevations of NA, ME, and NPY-LI adrenal plasma lev els (about 4 times) whereas A only increased twice. Clonidine decrease d catecholamine and ME adrenal plasma levels (the maximal percent decr ease when compared with control values was about 75%) whereas NPY adre nal plasma levels remained unchanged. In conclusion, the present data indicate that i) both adrenal ME and NA always exhibit corelease in a parallel fashion which is not the case for NPY and ii) different popul ations of chromaffin vesicles could be preferentially mobilized accord ing to different physiological and pharmacological patterns.