DIFFERENTIAL SECRETION OF CATECHOLAMINES IN RESPONSE TO PEPTIDERGIC AND CHOLINERGIC TRANSMITTERS IN RAT ADRENALS

1. Rat adrenal medulla is stimulated by cholinergic and peptidergic tr ansmitters released from splanchnic nerves. The peptidergic transmitte r has been identified as vasoactive intestinal polypeptide (VIP) and i ts contribution in comparison to that of acetylcholine (ACh) is more p rominent at low neuronal activity. The purpose of this study is to det ermine if ACh and VIP cause differential secretion of adrenaline and n oradrenaline and whether the differential secretion also occurs when s planchnic nerves are stimulated at different frequencies. 2. Perfusion of the left adrenal gland with Krebs solution for several hours did n ot change adrenaline and noradrenaline contents (15.2 mug and 3.5 mug, respectively) and their ratio (4.4) from those of the unperfused righ t adrenal medulla (15.2 mug, 3.3 mug and 4.8, respectively). 3. Perfus ion with ACh (10 muM for 4 min) resulted in the secretion of 109 ng of catecholamines and the ratio of adrenaline to noradrenaline was 3.8. Although the secretion increased with increased concentrations of ACh (30 and 100 muM), the ratios remained between 3 and 4. 4. Perfusion wi th VIP (10 muM for 4 min) resulted in the secretion of 27 ng of catech olamines and the ratio of adrenaline to noradrenaline was 9.7. A highe r concentration of VIP (20 muM for 4 min) resulted in the secretion of greater amounts of catecholamines (102 ng) without significantly alte ring the ratio of adrenaline to noradrenaline (10.9). 5. Perfusion wit h as low as 0.01 muM pituitary adenylate cyclase-activating polypeptid e (PACAP) increased the secretion of catecholamines to 31 ng and the s ecretion increased in a dose-dependent manner up to 0.3 muM. The ratio of adrenaline to noradrenaline was 6.8 with 0.1 muM PACAP and remaine d almost unchanged throughout the concentration range. 6. Electrical f ield stimulation at 0.5 Hz for 300 s resulted in the secretion of 34 n g catecholamines, and the ratio of adrenaline to noradrenaline was 6.9 . Delivering the same number of pulses at 1 Hz increased the secretion to 42 ng but reduced the ratio to 6.3. Increasing stimulation frequen cy to 10 Hz for 15 s or 30 s further increased the secretion to 66 ng and 180 ng, respectively, but significantly reduced the ratio to about 5. 7. Delivery of same number pulses at 3 Hz continuously or at 30 Hz in bursts caused a substantial reduction in catecholamine secretion ( 55 versus 35 ng) and in the ratio of adrenaline to noradrenaline (7.4 versus 5). 8. These results agree with the hypothesis that cholinergic and peptidergic transmitters control catecholamine secretion at diffe rent levels of neuronal activity and provide new evidence that ACh sti mulates the secretion of noradrenaline and adrenaline whereas VIP and PACAP predominantly stimulate the secretion of adrenaline.