Somatostatin, misoprostol and galanin inhibit gastrin- and PACAP-stimulated secretion of histamine and pancreastatin from ECL cells by blocking specific Ca(2+) channels.

Björkqvist, Maria; Lundgren, Maria; Eliasson, Lena; Håkanson, Rolf; Lindström, Erik

Somatostatin, misoprostol and galanin inhibit gastrin- and PACAP-stimulated secretion of histamine and pancreastatin from ECL cells by blocking specific Ca(2+) channels.

Mark

Björkqvist, Maria ^LU

; Lundgren, Maria ^LU ; Eliasson, Lena ^LU

; Håkanson, Rolf ^LU and Lindström, Erik (2005) In Regulatory Peptides 130(1-2). p.81-90

Abstract: The oxyntic mucosa is rich in ECL cells. They secrete histamine and chromogranin A-derived peptides, such as pancreastatin, in response to gastrin and pituitary adenylate cyclase-activating peptide (PACAP). Secretion is initiated by Ca2+ entry. While gastrin stimulates secretion by opening L-type and N-type Ca2+ channels, PACAP stimulates secretion by activating L-type and receptor-operated Ca2+ channels. Somatostatin, galanin and prostaglandin E2 (PGE2) inhibit gastrin- and PACAP-stimulated secretion from the ECL cells. In the present study, somatostatin and the PGE2 congener misoprostol inhibited gastrin- and PACAP-stimulated secretion 100%, while galanin inhibited at most 60–65%. Bay K 8644, a specific activator of L-type Ca2+ channels,... (More); The oxyntic mucosa is rich in ECL cells. They secrete histamine and chromogranin A-derived peptides, such as pancreastatin, in response to gastrin and pituitary adenylate cyclase-activating peptide (PACAP). Secretion is initiated by Ca2+ entry. While gastrin stimulates secretion by opening L-type and N-type Ca2+ channels, PACAP stimulates secretion by activating L-type and receptor-operated Ca2+ channels. Somatostatin, galanin and prostaglandin E2 (PGE2) inhibit gastrin- and PACAP-stimulated secretion from the ECL cells. In the present study, somatostatin and the PGE2 congener misoprostol inhibited gastrin- and PACAP-stimulated secretion 100%, while galanin inhibited at most 60–65%. Bay K 8644, a specific activator of L-type Ca2+ channels, stimulated ECL-cell secretion, an effect that was inhibited equally effectively by somatostatin, misoprostol and galanin (75–80% inhibition). Pretreatment with pertussis toxin, that inactivates inhibitory G-proteins, prevented all three agents from inhibiting stimulated secretion (regardless of the stimulus). Pretreatment with nifedipine (10 μM), an L-type Ca2+ channel blocker, reduced PACAP-evoked pancreastatin secretion by 50–60%, gastrin-evoked secretion by not, vert, similar 80% and abolished the response to Bay K 8644. The nifedipine-resistant response to PACAP was abolished by somatostatin and misoprostol but not by galanin. Gastrin and PACAP raised the intracellular Ca2+ concentration in a biphasic manner, believed to reflect mobilization of internal Ca2+ followed by Ca2+ entry. Somatostatin and misoprostol blocked Ca2+ entry (and histamine and pancreastatin secretion) but not mobilization of internal Ca2+.

The present observations on isolated ECL cells suggest that Ca2+ entry rather than mobilization of internal Ca2+ triggers exocytosis, that gastrin and PACAP activate different (but over-lapping) Ca2+ channels, that somatostatin, misoprostol and galanin interact with inhibitory G-proteins to block Ca2+ entry via L-type Ca2+ channels, and that somatostatin and misoprostol (but not galanin) in addition block N-type and/or receptor-operated Ca2+ channels. (Less)

Please use this url to cite or link to this publication: https://lup.lub.lu.se/record/140255

author

Björkqvist, Maria ^LU

; Lundgren, Maria ^LU ; Eliasson, Lena ^LU

; Håkanson, Rolf ^LU and Lindström, Erik

organization

publishing date

2005

type

Contribution to journal

publication status

published

subject

Cell and Molecular Biology

keywords

Gastrin, PACAP, Bay K 8644, PRL-2903, Galanin, Somatostatin, PGE2, Misoprostol

in

Regulatory Peptides

volume

130

issue

1-2

pages

81 - 90

publisher

Elsevier

external identifiers

wos:000230973700012
pmid:15935492
scopus:22044443032
pmid:15935492

ISSN

1873-1686

DOI

10.1016/j.regpep.2005.04.002

language

English

LU publication?

yes

id

13b9175d-c4d9-403d-9de9-ac4cde1b4835 (old id 140255)

alternative location

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15935492

date added to LUP

2016-04-01 12:31:41

date last changed

2023-09-02 10:51:53

@article{13b9175d-c4d9-403d-9de9-ac4cde1b4835,
  abstract     = {{The oxyntic mucosa is rich in ECL cells. They secrete histamine and chromogranin A-derived peptides, such as pancreastatin, in response to gastrin and pituitary adenylate cyclase-activating peptide (PACAP). Secretion is initiated by Ca2+ entry. While gastrin stimulates secretion by opening L-type and N-type Ca2+ channels, PACAP stimulates secretion by activating L-type and receptor-operated Ca2+ channels. Somatostatin, galanin and prostaglandin E2 (PGE2) inhibit gastrin- and PACAP-stimulated secretion from the ECL cells. In the present study, somatostatin and the PGE2 congener misoprostol inhibited gastrin- and PACAP-stimulated secretion 100%, while galanin inhibited at most 60–65%. Bay K 8644, a specific activator of L-type Ca2+ channels, stimulated ECL-cell secretion, an effect that was inhibited equally effectively by somatostatin, misoprostol and galanin (75–80% inhibition). Pretreatment with pertussis toxin, that inactivates inhibitory G-proteins, prevented all three agents from inhibiting stimulated secretion (regardless of the stimulus). Pretreatment with nifedipine (10 μM), an L-type Ca2+ channel blocker, reduced PACAP-evoked pancreastatin secretion by 50–60%, gastrin-evoked secretion by not, vert, similar 80% and abolished the response to Bay K 8644. The nifedipine-resistant response to PACAP was abolished by somatostatin and misoprostol but not by galanin. Gastrin and PACAP raised the intracellular Ca2+ concentration in a biphasic manner, believed to reflect mobilization of internal Ca2+ followed by Ca2+ entry. Somatostatin and misoprostol blocked Ca2+ entry (and histamine and pancreastatin secretion) but not mobilization of internal Ca2+.<br/><br>
<br/><br>
The present observations on isolated ECL cells suggest that Ca2+ entry rather than mobilization of internal Ca2+ triggers exocytosis, that gastrin and PACAP activate different (but over-lapping) Ca2+ channels, that somatostatin, misoprostol and galanin interact with inhibitory G-proteins to block Ca2+ entry via L-type Ca2+ channels, and that somatostatin and misoprostol (but not galanin) in addition block N-type and/or receptor-operated Ca2+ channels.}},
  author       = {{Björkqvist, Maria and Lundgren, Maria and Eliasson, Lena and Håkanson, Rolf and Lindström, Erik}},
  issn         = {{1873-1686}},
  keywords     = {{Gastrin; PACAP; Bay K 8644; PRL-2903; Galanin; Somatostatin; PGE2; Misoprostol}},
  language     = {{eng}},
  number       = {{1-2}},
  pages        = {{81--90}},
  publisher    = {{Elsevier}},
  series       = {{Regulatory Peptides}},
  title        = {{Somatostatin, misoprostol and galanin inhibit gastrin- and PACAP-stimulated secretion of histamine and pancreastatin from ECL cells by blocking specific Ca(2+) channels.}},
  url          = {{http://dx.doi.org/10.1016/j.regpep.2005.04.002}},
  doi          = {{10.1016/j.regpep.2005.04.002}},
  volume       = {{130}},
  year         = {{2005}},
}

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Somatostatin, misoprostol and galanin inhibit gastrin- and PACAP-stimulated secretion of histamine and pancreastatin from ECL cells by blocking specific Ca(2+) channels.