Abstract
The effect of neuropeptide Y [NPY(1–36)] and related peptides on the voltage-dependent currents and the nicotinic acetylcholine receptor (nAChR) currents (IACh) of bovine adrenal chromafptn cells was investigated using the whole-cell patch clamp technique. Catecholamine release from single chromaffin cells was measured by means of fast cyclic voltammetry. The potency order of these peptides in inhibiting IACh evoked by nicotine was NPY(1–36), NPY (16–36) > peptide YY(PYY) > [Leu31, Pro34] NPY. NPY(16–36) produced a similar degree of inhibition, irrespective of whether nicotine or an equipotent concentration of acetylcholine was used to evoke IACh. NPY(16–36) failed to alter voltage-dependent inward or outward currents. Intracellular cAMP, and extracellular dibutyryl-cAMP, produced a slowly developing increase in IACh. Intracellular cAMP, extracellular 8-Br-cAMP or dibutyryl-cAMP, and an inhibitor of cyclic nucleotide phosphodiesterases 3-isobutyl-l-methylxanthine (IBMX), decreased the inhibitory effect of NPY(16–36) on lACh. Although the intracellular application of the cAMP-dependent protein kinase A inhibitor [PKI(14–24)amide] alone did not alter IACh, it potentiated the effect of NPY(16–36) in interaction experiments. While the NPY(16–36)-induced inhibition of IACh was reversed on washout of the peptide, the slightly shorter C-terminal fragment NPY(18–36) caused a long-lasting depression of both IAch and catecholamine secretion evoked by nicotine. This depression was smaller in the presence of extracellular 8-Br-cAMP than in its absence. NPY(18–36) did not alter the secretory activity induced by a high concentration of potassium. It appears that, by activating Y3-receptors, NPY inhibits nAChR-current and the resulting secretion of catecholamines from bovine chromaffin cells. This process may involve a G protein-mediated decrease in intracellular cAMP with a subsequent decrease in the degree of phosphorylation of the nAChR-channel.
Similar content being viewed by others
References
Adams M, Boarder MR (1987) Secretion of [Met5]enkephalyl-Arg6-Phe7-related peptides and catecholamines from bovine adrenal chromaffin cells: modification by changes in cyclic AMP and by treatment with reserpine. J Neurochem 49:208–215
Allen JM, Bloom SR (1986) Neuropeptide Y: a putative transmitter. Neurochem Int 8:1–8
Allen JM, Bircham, PMM, Bloom SR, Edwards AV (1984) Release of neuropeptide Y in response to splanchnic nerve stimulation in the conscious calf. J Physiol (Lond) 357:401–408
Allen YS, Adrian TE, Allen JM, Tatemoto K, Crow TJ, Bloom SR, Polak JM (1983) Neuropeptide Y distribution in the rat brain. Science 221:877–879
Anderson K, Robinson PJ, Marley PD (1992) Cholinoceptor regulation of cyclic AMP levels in bovine adrenal medullary cells. Br J Pharmacol 106:360–366
Balasubramaniam A, Sheriff S (1990) Neuropeptide Y(18–36) is a competitive antagonist of neuropeptide Y in rat cardiac ventricular membranes. J Biol Chem 265:14724–14727
Bastiaensen E, De Block J, De Potter WP (1988) Neuropeptide Y is localized together with enkephalins in adrenergic granules of bovine chromaffin cells. Neuroscience 25:679–686
Beavo JA, Reifsnyder DH (1990) Primary sequence of cyclic nucleotide phosphodiesterase isozymes and the design of selective inhibitors. Trends Pharmacol Sci 11:150–155
Bormann J, Flügge G, Fuchs E (1989) Effect of atrial natriuretic factor (ANF) on nicotinic acetylcholine receptor channels in bovine chromaffin cells. Pflügers Arch 414:11–14
Cena V, Nicolas GP, Sanchez-Garcia P, Kirpekar SM, Garcia AG (1983) Pharmacological dissection of receptor-associated and voltage-sensitive ionic channels involved in catecholamine release. Neuroscience 10:1455–1462
Cheng H-C, Kemp BE, Pearson RB, Smith AJ, Misconi L, Van Patten SM, Walsh DA (1986) A potent synthetic peptide inhibitor of the cAMP-dependent protein kinase. J Biol Chem 261:989–992
Colquhoun D, Ogden DC, Mathie A (1987) Nicotinic acetylcholine receptors of nerve and muscle: functional aspects. Trends Pharmacol Sci 8:465–472
Cubeddu L, Weiner N (1975) Release of norepinephrine and dopamine- \-hydroxylase by nerve stimulation. V. Enhanced release associated with a granular effect of a benzoquinolizine derivative with reserpine-like properties. J Pharmacol Exp Ther 193:757–774
Cull-Candy SG, Mathie A, Powis DA (1988) Acetylcholine receptor channels and their block by clonidine in cultured bovine chromaffin cells. J Physiol (Lond) 402:255–278
Douglas WW, Rubin RP (1963) The mechanism of catecholamine release from adrenal medulla and the role of calcium in stimulus-secretion coupling. J Physiol (Lond) 167:288–310
Grant NJ, Aunis D, Bader M-F (1987) Morphology and secretory activity of digitonin- and α-toxin-permeabilized chromaffin cells. Neuroscience 10:1143–1155
Hamill OP, Marty A, Neher E, Sakmann B, Sigworth FJ (1981) Improved patch-clamp techniques for high resolution current recording from cells and cell-free membrane patches. Pflugers Arch 319:85–100
Hexum TD, Majane EA, Russett LR, Yang H-YT (1987) Neuropeptide Y release from the adrenal medulla after cholinergic receptor stimulation. J Pharmacol Exp Ther 243:927–930
Higgins LS, Berg DK (1988) Cyclic AMP-dependent mechanism regulates acetylcholine receptor function on bovine adrenal chromaffin cells and discriminates between new and old receptors. J Cell Biol 107:1157–1165
Higuchi H, Costa E, Yang H-YT (1988) Neuropeptide Y inhibits the nicotine-mediated release of catecholamines from bovine adrenal chromaffin cells. J Pharmacol Exp Ther 244:468–474
Huganir RL, Greengard P (1987) Regulation of receptor function by protein phosphorylation. Trends Pharmacol Sci 8:472–477
Huganir RL, Delcour AH, Greengard P, Hess GP (1986) Phosphorylation of the nicotinic acetylcholine receptor regulates its rate of desensitization. Nature 321:774–776
Illes P (1986) Mechanisms of receptor-mediated modulation of transmitter release in noradrenergic, cholinergic and sensory neurones. Neuroscience 17:909–928
Illes P, Regenold JT (1990) Interaction between neuropeptide Y and noradrenaline on central catecholamine neurons. Nature 344:62–63
Kataoka Y, Majane EA, Yang H-YT (1985) Release of NPY-like immunoreactive material from primary cultures of chromaffin cells prepared from bovine adrenal medulla. Neuropharmacology 24:693–695
Keogh R, Marley PD (1991) Regulation of cyclic AMP levels by calcium in bovine adrenal medullary cells. J Neurochem 57:1721–1728
Limberger N, Trout SJ, Kruk ZL, Starke K (1991) “Real time” measurement of endogenous dopamine release during short trains of pulses in slices of rat neostriatum and nucleus accumbens: role of autoinhibition. Naunyn Schmiedebergs Arch Pharmacol 344:623–629
Lundberg JM, Terenius L, Hökfelt T, Martling CL, Tatemoto K, Mutt V, Polak J, Bloom SR, Goldstein M (1982) Neuropeptide Y (NPY)-like immunoreactivity in peripheral noradrenergic neurones and effects of NPY on sympathetic function. Acta Physiol Scand 116:477–480
Majane EA, Alho A, Kataoka Y, Lee CH, Yang H-YT (1985) Neuropeptide Y in bovine adrenal glands: distribution and characterization. Endocrinology 117:1162–1168
Margiotta JF, Berg DK, Dionne VE (1987) Cyclic AMP regulates the proportion of functional acetylcholine receptors on chicken ciliary ganglion neurons. Proc Natl Acad Sci USA 84:8155–8159
Marley PD, Thompson KA (1992) Regulation of cyclic AMP metabolism in bovine adrenal medullary cells. Biochem Pharmacol 11:2105–2110
Marty A, Neher E (1985) Potassium channels in cultured bovine adrenal chromaffin cells. J Physiol (Lond) 367:117–141
Michel MC (1991) Receptors for neuropeptide Y: multiple subtypes and multiple second messengers. Trends Pharmacol Sci 12:389–394
Morita K, Dohi T, Kitayama S, Koyama Y, Tsujimoto A (1987) Enhancement of stimulation-evoked catecholamine release from cultured bovine adrenal chromaffin cells by forskolin. J Neurochem 48:243–247
Nooney JM, Lambert JJ, Chiappinelli VA (1992a) The interaction of κ-bungarotoxin with the nicotinic receptor of bovine chromaffin cells. Brain Res 573:77–82
Nooney JM, Peters JA, Lambert JJ (1992b) A patch clamp study of the nicotinic acetylcholine receptor of bovine adrenomedullary chromaffin cells in culture. J Physiol (Lond) 455:503–527
Nörenberg W, Illes P, Takeda K (1991) Neuropeptide Y inhibits nicotinic cholinergic currents but not voltage-dependent calcium currents in bovine chromaffin cells. Pflugers Arch 418:346–352
Powis DA, Baker PF (1986) α2-Adrenoceptors do not regulate catecholamine secretion in bovine adrenal medullary cells: a study with clonidine. Mol Pharmacol 29:134–141
Sargent PB (1993) The diversity of neuronal nicotinic acetylcholine receptors. Annu Rev Neurosci 16:403–443
Schwartz TW, Fuhlendorff J, Langeland N, Thogersen H, Jorgensen JC, Sheikh SP (1989) Y1 and Y2 receptors for NPY - the evolution of PP-fold peptides and their receptors. In: Mutt V, Fuxe K, Hökfelt T, Lundberg JM (eds) Neuropeptide Y, Karolinska Institute Nobel Conference Series. Raven Press, New York, pp. 143–151
Schofield GG, Ikeda SR (1988) Neuropeptide Y blocks a calcium current in C cells of bullfrog sympathetic ganglia. Eur J Pharmacol 151:131–134
Sontag J-M, Sanderson P, Klepper M, Aunis D, Takeda K, Bader M-F (1990) Modulation of secretion by dopamine involves decreases in calcium and nicotinic currents in bovine chromaffin cells. J Physiol (Lond) 427:495–517
Tatemoto K, Carlquist M, Mutt V (1982) Neuropeptide Y - a novel brain peptide with structural similarities to peptide YY and pancreatic polypeptide. Nature 296:659–660
Vijayaraghavan S, Schmid HA, Halvorsen SW, Berg DK (1990) Cyclic AMP-dependent phosphorylation of a neuronal acetylcholine receptor α-type unit. J Neurosci 10:3255–3262
Wahlestedt C, Regunathan S, Reis DJ (1992) Identification of cultured cells selectively expressing Y1-, Y2-, or Y3-type receptors for neuropeptide Y/peptide YY. Life Sci 50:7–12
Walaas SI, Greengard P (1991) Protein phosphorylation and neuronal function. Pharmacol Rev 43:299–349
Walker P, Grouzmann E, Burnier M, Waeber B (1991) The role of neuropeptide Y in cardiovascular regulation. Trends Pharmacol Sci 12:111–115
Wightman RM, Jankowski JA, Kennedy RT, Kawagoe KT, Schroeder TJ, Leszczyszyn DJ, Near JA, Diliberto JR EJ, Viveros OH (1991) Temporally resolved catecholamine spikes correspond to single vesicle release from individual chromaffin cells. Proc Natl Acad Sci USA 88:10754–10758
Wiley JW, Gross RA, Lu Y, MacDonald RL (1990) Neuropeptide Y reduces calcium currents and inhibits acetylcholine release in nodose neurons via a pertussis toxin-sensitive mechanism. J Neurophysiol 63:1499–1507
Zhu J, Li W, Toews ML, Hexum TD (1992) Neuropeptide Y inhibits forskolin-stimulated adenylate cyclase in bovine adrenal chromaffin cells via a pertussis toxin-sensitive process. J Pharmacol Exp Ther 263:1479–1486
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Nörenberg, W., Bek, M., Limberger, N. et al. Inhibition of nicotinic acetylcholine receptor channels in bovine adrenal chromaffin cells by Y3-type neuropeptide Y receptors via the adenylate cyclase/protein kinase A system. Naunyn-Schmiedeberg's Arch Pharmacol 351, 337–347 (1995). https://doi.org/10.1007/BF00169073
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00169073