PACAP and acetylcholine cause distinct Ca2+ signals and secretory responses in chromaffin cells.
Journal
The Journal of general physiology
ISSN: 1540-7748
Titre abrégé: J Gen Physiol
Pays: United States
ID NLM: 2985110R
Informations de publication
Date de publication:
06 02 2023
06 02 2023
Historique:
received:
21
04
2022
revised:
22
09
2022
revised:
12
11
2022
accepted:
18
11
2022
entrez:
20
12
2022
pubmed:
21
12
2022
medline:
23
12
2022
Statut:
ppublish
Résumé
The adrenomedullary chromaffin cell transduces chemical messages into outputs that regulate end organ function throughout the periphery. At least two important neurotransmitters are released by innervating preganglionic neurons to stimulate exocytosis in the chromaffin cell-acetylcholine (ACh) and pituitary adenylate cyclase activating polypeptide (PACAP). Although PACAP is widely acknowledged as an important secretagogue in this system, the pathway coupling PACAP stimulation to chromaffin cell secretion is poorly understood. The goal of this study is to address this knowledge gap. Here, it is shown that PACAP activates a Gαs-coupled pathway that must signal through phospholipase C ε (PLCε) to drive Ca2+ entry and exocytosis. PACAP stimulation causes a complex pattern of Ca2+ signals in chromaffin cells, leading to a sustained secretory response that is kinetically distinct from the form stimulated by ACh. Exocytosis caused by PACAP is associated with slower release of peptide cargo than exocytosis stimulated by ACh. Importantly, only the secretory response to PACAP, not ACh, is eliminated in cells lacking PLCε expression. The data show that ACh and PACAP, acting through distinct signaling pathways, enable nuanced and variable secretory outputs from chromaffin cells.
Identifiants
pubmed: 36538657
pii: 213771
doi: 10.1085/jgp.202213180
pmc: PMC9770323
pii:
doi:
Substances chimiques
Pituitary Adenylate Cyclase-Activating Polypeptide
0
Acetylcholine
N9YNS0M02X
Calcium
SY7Q814VUP
Catecholamines
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : American Heart Association-American Stroke Association
ID : 17GRNT33661156
Pays : United States
Organisme : NIGMS NIH HHS
ID : R35 GM127303
Pays : United States
Organisme : NIDA NIH HHS
ID : R37 DA039997
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS122534
Pays : United States
Organisme : NIH HHS
ID : R37DA0333987
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM111997
Pays : United States
Informations de copyright
© 2022 Morales et al.
Références
Islets. 2011 May-Jun;3(3):121-8
pubmed: 21478675
Nat Commun. 2015 Jul 09;6:7670
pubmed: 26158227
J Neurochem. 1988 Apr;50(4):1302-8
pubmed: 2894411
J Physiol. 1958 Apr 3;141(1):97-106
pubmed: 13539823
J Biol Chem. 2007 Mar 16;282(11):8079-91
pubmed: 17213203
Peptides. 2011 Aug;32(8):1647-55
pubmed: 21693142
J Neurosci. 2013 May 1;33(18):8068-78
pubmed: 23637196
Mol Biol Cell. 2011 Jun 1;22(11):1907-18
pubmed: 21460182
Acta Pharmacol Sin. 2012 Mar;33(3):372-84
pubmed: 22266728
J Neurochem. 1996 Jul;67(1):155-62
pubmed: 8666986
Endocrinology. 2013 Jan;154(1):330-9
pubmed: 23221599
Compr Physiol. 2019 Sep 19;9(4):1443-1502
pubmed: 31688964
Mol Cell Neurosci. 2010 Feb;43(2):244-57
pubmed: 19958833
Pharmacol Ther. 2009 Mar;121(3):294-316
pubmed: 19109992
Endocrinology. 1996 Mar;137(3):956-66
pubmed: 8603609
Mol Cell Neurosci. 2017 Dec;85:170-182
pubmed: 29017814
Br J Pharmacol. 1968 Nov;34(3):451-74
pubmed: 4882190
J Gen Physiol. 2017 Oct 2;149(10):921-934
pubmed: 28882880
J Physiol. 1994 Mar 15;475(3):539-45
pubmed: 8006835
Sci Signal. 2017 Jan 24;10(463):
pubmed: 28119465
Biochim Biophys Acta. 1985 Jul 30;846(1):167-73
pubmed: 3893551
J Neurochem. 2009 Aug;110(4):1214-25
pubmed: 19508428
Acta Physiol (Oxf). 2008 Feb;192(2):287-301
pubmed: 18005392
Nat Neurosci. 2010 Jun;13(6):759-66
pubmed: 20495558
Proc Natl Acad Sci U S A. 2002 Jan 8;99(1):461-6
pubmed: 11756684
J Neurocytol. 1974 Aug;3(3):341-61
pubmed: 4140222
Biochem Biophys Res Commun. 1989 Oct 16;164(1):567-74
pubmed: 2803320
J Physiol. 2021 Mar;599(6):1855-1883
pubmed: 33450050
J Mol Neurosci. 2012 Oct;48(2):403-12
pubmed: 22610912
Stress. 2007 Jun;10(2):109-20
pubmed: 17514579
J Biol Chem. 2009 Jan 16;284(3):1514-22
pubmed: 18957419
Radiother Oncol. 2015 Nov;117(2):234-9
pubmed: 26306677
Cell. 2013 Mar 28;153(1):216-27
pubmed: 23540699
Stat Med. 2017 Jun 30;36(14):2187-2205
pubmed: 28276584
Physiol Rev. 2006 Oct;86(4):1093-131
pubmed: 17015485
Acta Physiol (Oxf). 2008 Feb;192(2):213-20
pubmed: 18021321
Mol Biol Cell. 2018 Apr 1;29(7):834-845
pubmed: 29444959
J Biophys Biochem Cytol. 1957 Jul 25;3(4):611-4
pubmed: 13449104
Nature. 1993 Sep 9;365(6442):170-5
pubmed: 8396727
Pflugers Arch. 2018 Jan;470(1):79-88
pubmed: 28965274
Biochem Pharmacol. 1985 May 1;34(9):1497-500
pubmed: 3994761
Mol Pharmacol. 2013 Jan;83(1):122-8
pubmed: 23066090
J Biol Chem. 1996 May 3;271(18):10545-50
pubmed: 8631854
J Neurochem. 1981 Aug;37(2):491-7
pubmed: 7264672
J Biol Chem. 2011 Jul 1;286(26):23012-21
pubmed: 21550986
Biophys J. 2006 Mar 1;90(5):1830-41
pubmed: 16361341
J Gen Physiol. 2017 Aug 7;149(8):763-780
pubmed: 28687607
J Neurosci. 1997 Apr 1;17(7):2314-23
pubmed: 9065492
J Neurosci. 2012 Oct 3;32(40):13819-40
pubmed: 23035093
J Biol Chem. 2011 Dec 9;286(49):42459-42469
pubmed: 22009744
Neuropharmacology. 2016 Nov;110(Pt A):438-448
pubmed: 27544824
J Physiol. 2017 Nov 15;595(22):6851-6867
pubmed: 28944482
J Biol Chem. 1985 Mar 25;260(6):3440-50
pubmed: 3838314
IUBMB Life. 2020 Apr;72(4):553-567
pubmed: 31301221
Cell Mol Neurobiol. 2010 Nov;30(8):1433-40
pubmed: 21061156
Science. 2009 Jun 12;324(5933):1441-4
pubmed: 19423778
Neuroscience. 1994 Mar;59(1):1-5
pubmed: 7910672
Elife. 2021 Mar 22;10:
pubmed: 33749593
J Neurochem. 2020 Sep;154(6):598-617
pubmed: 32058590
J Neurosci. 2010 Jan 13;30(2):491-504
pubmed: 20071512
Cell Signal. 2012 Jun;24(6):1333-43
pubmed: 22286105
J Physiol. 1982 Mar;324:203-20
pubmed: 7097596
Elife. 2019 May 20;8:
pubmed: 31099751
J Gen Physiol. 2018 Jun 4;150(6):783-807
pubmed: 29794152
Mol Psychiatry. 2015 Jul;20(7):810-9
pubmed: 25939402
J Gen Physiol. 2019 Feb 4;151(2):118-130
pubmed: 30504267
Circ Res. 2005 Dec 9;97(12):1305-13
pubmed: 16293787
Bull N Y Acad Med. 1940 Jan;16(1):3-13
pubmed: 19312138
J Neurophysiol. 2002 Sep;88(3):1374-86
pubmed: 12205158
J Biol Chem. 2004 Nov 5;279(45):47115-24
pubmed: 15331588
Nat Cell Biol. 2001 Nov;3(11):1020-4
pubmed: 11715024
J Physiol. 2010 Dec 15;588(Pt 24):4871-89
pubmed: 21041529
J Neurosci. 1999 Jan 1;19(1):206-19
pubmed: 9870951
J Neurochem. 2001 Sep;78(6):1243-55
pubmed: 11579133
J Gen Physiol. 2019 Apr 1;151(4):417-434
pubmed: 30782604
J Neurosci. 2005 Dec 7;25(49):11374-84
pubmed: 16339032
Arch Biochem Biophys. 2008 Sep 1;477(1):146-54
pubmed: 18492483
J Biol Chem. 2007 Feb 23;282(8):5488-95
pubmed: 17178726
Brain Neurosci Adv. 2018 Oct 2;2:
pubmed: 30320224
Pflugers Arch. 2018 Jan;470(1):39-52
pubmed: 28776261
Front Endocrinol (Lausanne). 2013 May 21;4:55
pubmed: 23734144
J Neurochem. 2016 Dec;139(5):722-736
pubmed: 27649809
J Physiol. 2004 Jul 15;558(Pt 2):433-49
pubmed: 15133061
Physiol Rep. 2016 Sep;4(17):
pubmed: 27597763