PACAP Activates Calcium Influx-dependent and -independent Pathways to Couple Met-enkephalin Secretion and Biosynthesis in Chromaffin Cells

Overview

Journal J Mol Neurosci

Specialties Molecular Biology
Neurology

Date 1998 Nov 25

PMID 9826785

Citations 12

Authors

S H Hahm

C M Hsu

L E Eiden

Affiliations

Soon will be listed here.

Abstract

Pituitary adenylate cyclase activating polypeptide-27 (PACAP-27) caused a dose-dependent increase in met-enkephalin secretion and increased production of met-enkephalin peptide and proenkephalin A (PEnk) mRNA in bovine chromaffin cells, at concentrations as low as 300 pM. PACAP-38 was less potent than PACAP-27, but had similar effects. Vasoactive intestinal polypeptide (VIP) (1-100 nM) was without appreciable effect on either enkephalin secretion or biosynthesis, implicating PACAP type I receptors in PACAP-stimulated enkephalin secretion and synthesis. PACAP type I receptors can activate adenylate cyclase and stimulate phospholipase C through heterotrimeric G protein interactions, leading to increased intracellular cyclic AMP (cAMP), inositol triphosphate (IP3)-mediated calcium mobilization, and calcium- and diacylglycerol (DAG)-mediated protein kinase C (PKC) activation. Enkephalin secretion evoked by 10-100 nM PACAP-27 was not inhibited by 1 microM (-)-202-791, an L-type specific dihydropyridine calcium channel blocker, but was inhibited 65-80% by the arylalkylamine calcium channel blocker D600. Forty mM potassium-evoked secretion was inhibited > 90% by both D600 and (-)-202-791, 25 microM forskolin-induced secretion was blocked < 50% by D600 and was unaffected by (-)-202-791, and 100 nM phorbol myristate acetate (PMA)-induced secretion was unaffected by either D600 or (-)-202-791. Enkephalin biosynthesis was increased by 10 nM PACAP-27, as measured by increased met-enkephalin pentapeptide content and PEnk A mRNA levels. PACAP-, forskolin-, and PMA-stimulated enkephalin synthesis were not blocked by D600 or (-)-202-791. Elevated potassium-induced enkephalin biosynthesis upregulation was completely blocked by either D600 or (-)-202-791 at the same concentrations. PACAP acting through type I PACAP receptors couples calcium influx-dependent enkephalin secretion and calcium influx-independent enkephalin biosynthesis in chromaffin cells. Restriction of the effects of enhanced calcium influx to stimulation of secretion, but not of biosynthesis, is unique to PACAP. By contrast, potassium-induced enkephalin biosynthesis upregulation is completely calcium influx dependent, specifically via calcium influx through L-type calcium channels. We propose that subpopulations of voltage-dependent calcium channels are differentially linked to intracellular signal transduction pathways that control neuropeptide gene expression and secretion in chromaffin cells.

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References

Eiden L, Hotchkiss A . Cyclic adenosine monophosphate regulates vasoactive intestinal polypeptide and enkephalin biosynthesis in cultured bovine chromaffin cells. Neuropeptides. 1983; 4(1):1-9. DOI: 10.1016/0143-4179(83)90002-1. View

DOUGLAS W, Rubin R . The role of calcium in the secretory response of the adrenal medulla to acetylcholine. J Physiol. 1961; 159:40-57. PMC: 1359576. DOI: 10.1113/jphysiol.1961.sp006791. View

Wakade A . Multiple transmitter control of catecholamine secretion in rat adrenal medulla. Adv Pharmacol. 1997; 42:595-8. DOI: 10.1016/s1054-3589(08)60821-2. View

OFarrell M, Ziogas J, Marley P . Effects of N- and L-type calcium channel antagonists and (+/-)-Bay K8644 on nerve-induced catecholamine secretion from bovine perfused adrenal glands. Br J Pharmacol. 1997; 121(3):381-8. PMC: 1564695. DOI: 10.1038/sj.bjp.0701131. View

Quach T, Tang F, Kageyama H, Mocchetti I, Guidotti A, Meek J . Enkephalin biosynthesis in adrenal medulla. Modulation of proenkephalin mRNA content of cultured chromaffin cells by 8-bromo-adenosine 3',5'-monophosphate. Mol Pharmacol. 1984; 26(2):255-60. View

Bommer M, Liebisch D, Kley N, Herz A, Noble E . Histamine affects release and biosynthesis of opioid peptides primarily via H1-receptors in bovine chromaffin cells. J Neurochem. 1987; 49(6):1688-96. DOI: 10.1111/j.1471-4159.1987.tb02426.x. View

Lopez M, Villarroya M, Lara B, Martinez Sierra R, Albillos A, Garcia A . Q- and L-type Ca2+ channels dominate the control of secretion in bovine chromaffin cells. FEBS Lett. 1994; 349(3):331-7. DOI: 10.1016/0014-5793(94)00696-2. View

Corcoran J, Kirshner N . Inhibition of calcium uptake, sodium uptake, and catecholamine secretion by methoxyverapamil (D600) in primary cultures of adrenal medulla cells. J Neurochem. 1983; 40(4):1106-9. DOI: 10.1111/j.1471-4159.1983.tb08099.x. View

MacArthur L, Koller K, Eiden L . Enkephalin gene transcription in bovine chromaffin cells is regulated by calcium and protein kinase A signal transduction pathways: identification of DNase I-hypersensitive sites. Mol Pharmacol. 1993; 44(3):545-51. View

10.

Babinski K, Bodart V, Roy M, De Lean A, Ong H . Pituitary adenylate-cyclase activating polypeptide (PACAP) evokes long-lasting secretion and de novo biosynthesis of bovine adrenal medullary neuropeptides. Neuropeptides. 1996; 30(6):572-82. DOI: 10.1016/s0143-4179(96)90041-4. View

11.

Eiden L, Giraud P, Dave J, Hotchkiss A, Affolter H . Nicotinic receptor stimulation activates enkephalin release and biosynthesis in adrenal chromaffin cells. Nature. 1984; 312(5995):661-3. DOI: 10.1038/312661a0. View

12.

Lomax R, Michelena P, Nunez L, Garcia-Sancho J, Garcia A, Montiel C . Different contributions of L- and Q-type Ca2+ channels to Ca2+ signals and secretion in chromaffin cell subtypes. Am J Physiol. 1997; 272(2 Pt 1):C476-84. DOI: 10.1152/ajpcell.1997.272.2.C476. View

13.

Fischer-Colbrie R, Gutierrez J, Hsu C, Iacangelo A, Eiden L . Sequence analysis, tissue distribution and regulation by cell depolarization, and second messengers of bovine secretogranin II (chromogranin C) mRNA. J Biol Chem. 1990; 265(16):9208-13. View

14.

Wilson S . Vasoactive intestinal peptide and substance P increase levels of enkephalin-containing peptides in adrenal chromaffin cells. Life Sci. 1987; 40(7):623-8. DOI: 10.1016/0024-3205(87)90262-1. View

15.

Muller A, Monnier D, Rene F, Larmet Y, Koch B, Loeffler J . Pituitary adenylate cyclase-activating polypeptide triggers dual transduction signaling in CATH.a cells and transcriptionally activates tyrosine hydroxylase and c-fos expression. J Neurochem. 1997; 68(4):1696-704. DOI: 10.1046/j.1471-4159.1997.68041696.x. View

16.

Rius R, Guidotti A, Costa E . Pituitary adenylate cyclase activating polypeptide (PACAP) potently enhances tyrosine hydroxylase (TH) expression in adrenal chromaffin cells. Life Sci. 1994; 54(22):1735-43. DOI: 10.1016/0024-3205(94)00614-8. View

17.

Wan D, Marley P, Livett B . Coordinate and differential regulation of proenkephalin A and PNMT mRNA expression in cultured bovine adrenal chromaffin cells: responses to cAMP elevation and phorbol esters. Brain Res Mol Brain Res. 1991; 9(1-2):135-42. DOI: 10.1016/0169-328x(91)90138-n. View

18.

Tonshoff C, Hemmick L, Evinger M . Pituitary adenylate cyclase activating polypeptide (PACAP) regulates expression of catecholamine biosynthetic enzyme genes in bovine adrenal chromaffin cells. J Mol Neurosci. 1998; 9(2):127-40. DOI: 10.1007/BF02736856. View

19.

Comb M, Birnberg N, Seasholtz A, Herbert E, Goodman H . A cyclic AMP- and phorbol ester-inducible DNA element. Nature. 1986; 323(6086):353-6. DOI: 10.1038/323353a0. View

20.

Farin C, Kley N, Hollt V . Mechanisms involved in the transcriptional activation of proenkephalin gene expression in bovine chromaffin cells. J Biol Chem. 1990; 265(31):19116-21. View