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Contribution of acetylcholine and vasoactive intestinal polypeptide in controlling catecholamine secretion
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findings is that clonidine may not modulate calcium entry directly through c~2-adrenoceptors as presently believed but may act at some step involved in depolarization-secretion coupling. Clearly there are other possible explanations and further studies are required to establish whether PDBu leads to, for example, phosphorylation of the c~2-adrenoceptor which then uncouples the a2-adrenoceptor from calcium channels and hence alters calcium entry indirectly.
References 1 Brock. J.A. and Cunnane, T.('., J. Physiol.. 39t9 (1988) 602 632. 2 Lipscombe, D., Kongsamut, S. and Tsien, R.W.. N~ture 340 (1989) 639-642. 3 Malenka, R.C., Madison, D.V. and Nicoll, R.A., Nature 321 (1986) 175-177. 4 Musgrave, I.F. and Majewski, H., Naunyn-Schmiedeberg's Arch. Pharm., 339 (1989) 48-53. 5 Wood, J.G.. Girad, P.R., Mazzei, O.J. and Kuo. J.F...I. Neurosci., 6 (1986) 2571-2577.
C.F.W. is a Squibb Research Scholar.
Contribution of acetyicholine and vasoactive intestinal pe~ypeptide in controlling c a t e c h o t a m ~ secretion Arun R. Wakade Department of Pharmacology, School of Medicine, Wayne State University, Detroit, M I 48201, U.S.A.
Our physiological and pharmacological studies have shown that secretion of adrenal medullary hormones is regulated by multiple neurotransmitters released from splanchnic nerve terminals of the rat [1,2]. From these and other studies we proposed that, in addition to the classical neurotransmitter acetylcholine (ACh), vasoactive intestinal polypeptide (VIP) may contribute to the stimulation of chromaffin cells and induce secretion of catecholamines (CA). The purpose of the present investigation was to determine the relative contribution of ACh and VIP at different levels of neuronal activity in regulating the secretion of CA. Field stimulation of splanchnic neurones caused release of VIP-like immunoreactivity (VIPLI), determined by radioimmunoassay, in the perfusate of the isolated adrenal gland of the rat. The release was inversely related to the frequency of stimulation (8.6 x 1 0 - 3 , 4.9 x 1 0 - 3 and 4.0 x 10 3 f m o l / p u l s e at 1, 3 and 10 Hz, respectively). Release of ACh was determined by loading the gland with 3H-choline and separating 3H-ACh from the total tritium in the perfusate. Field stimulation produced a significant increase in the release of
3H-ACh over the spontaneous release. The stimulation-evoked fractional release of 3H-ACh was directly related to the frequency of stimulation ( 4 . 5 x 1 0 2 at 1 Hz for 5 min and 7 . 4 x i 0 - 2 at 10 Hz for 30 sec). Release of VIP-LI and 3H-ACh was abolished by omission of C a C I : from the perfusing medium and by Ca + +-channel blockers. After chronic ablation of splanchnic nerves, field stimulation of the adrenal gland did not evoke release of either VIP. 3H-ACh or CA, although infusion of exogenous ACh or VIP produced secretion of CA. These results provide direct evidence for the release of ACh and VIP from the splanchnic nerve endings in the rat adrenal medulla. Of additional importance is the finding that ACh release predominates at higher frequencies whereas release of VIP declines with increasing neural activity.
References 1 Malhotra, R.K. and Wakade, A.R.. J. Physiol., 383 ~19871 639-652. 2 Wakade. A.R.. J Neurochem. 50. (1988~ 1302-1308.
findings is that clonidine may not modulate calcium entry directly through c~2-adrenoceptors as presently believed but may act at some step involved in depolarization-secretion coupling. Clearly there are other possible explanations and further studies are required to establish whether PDBu leads to, for example, phosphorylation of the c~2-adrenoceptor which then uncouples the a2-adrenoceptor from calcium channels and hence alters calcium entry indirectly.
References 1 Brock. J.A. and Cunnane, T.('., J. Physiol.. 39t9 (1988) 602 632. 2 Lipscombe, D., Kongsamut, S. and Tsien, R.W.. N~ture 340 (1989) 639-642. 3 Malenka, R.C., Madison, D.V. and Nicoll, R.A., Nature 321 (1986) 175-177. 4 Musgrave, I.F. and Majewski, H., Naunyn-Schmiedeberg's Arch. Pharm., 339 (1989) 48-53. 5 Wood, J.G.. Girad, P.R., Mazzei, O.J. and Kuo. J.F...I. Neurosci., 6 (1986) 2571-2577.
C.F.W. is a Squibb Research Scholar.
Contribution of acetyicholine and vasoactive intestinal pe~ypeptide in controlling c a t e c h o t a m ~ secretion Arun R. Wakade Department of Pharmacology, School of Medicine, Wayne State University, Detroit, M I 48201, U.S.A.
Our physiological and pharmacological studies have shown that secretion of adrenal medullary hormones is regulated by multiple neurotransmitters released from splanchnic nerve terminals of the rat [1,2]. From these and other studies we proposed that, in addition to the classical neurotransmitter acetylcholine (ACh), vasoactive intestinal polypeptide (VIP) may contribute to the stimulation of chromaffin cells and induce secretion of catecholamines (CA). The purpose of the present investigation was to determine the relative contribution of ACh and VIP at different levels of neuronal activity in regulating the secretion of CA. Field stimulation of splanchnic neurones caused release of VIP-like immunoreactivity (VIPLI), determined by radioimmunoassay, in the perfusate of the isolated adrenal gland of the rat. The release was inversely related to the frequency of stimulation (8.6 x 1 0 - 3 , 4.9 x 1 0 - 3 and 4.0 x 10 3 f m o l / p u l s e at 1, 3 and 10 Hz, respectively). Release of ACh was determined by loading the gland with 3H-choline and separating 3H-ACh from the total tritium in the perfusate. Field stimulation produced a significant increase in the release of
3H-ACh over the spontaneous release. The stimulation-evoked fractional release of 3H-ACh was directly related to the frequency of stimulation ( 4 . 5 x 1 0 2 at 1 Hz for 5 min and 7 . 4 x i 0 - 2 at 10 Hz for 30 sec). Release of VIP-LI and 3H-ACh was abolished by omission of C a C I : from the perfusing medium and by Ca + +-channel blockers. After chronic ablation of splanchnic nerves, field stimulation of the adrenal gland did not evoke release of either VIP. 3H-ACh or CA, although infusion of exogenous ACh or VIP produced secretion of CA. These results provide direct evidence for the release of ACh and VIP from the splanchnic nerve endings in the rat adrenal medulla. Of additional importance is the finding that ACh release predominates at higher frequencies whereas release of VIP declines with increasing neural activity.
References 1 Malhotra, R.K. and Wakade, A.R.. J. Physiol., 383 ~19871 639-652. 2 Wakade. A.R.. J Neurochem. 50. (1988~ 1302-1308.