Gastrin and the neuropeptide PACAP evoke secretion from rat stomach histamine-containing (ECL) cells by stimulating influx of Ca2+ through different Ca2+ channels
Lindström, Erik ; Eliasson, Lena LU
; Björkqvist, Maria
LU
and Håkanson, Rolf
LU
(2001)
In Journal of Physiology
535(3).
p.663-677
- Abstract
- Gastrin and PACAP stimulate secretion of histamine and pancreastatin from isolated rat stomach ECL cells. We have examined whether or not secretion depends on the free cytosolic Ca2+ concentration ([Ca2+i) and the pathways by which gastrin and PACAP elevate [Ca2+i. Secretion was monitored by radioimmunoassay of pancreastatin and changes in [Ca2+i by video imaging. The patch clamp technique was used to record whole-cell currents and membrane capacitance (reflecting exocytosis). In the presence of 2 mM extracellular Ca2+, gastrin and PACAP induced secretion and raised [Ca2+i. Without extracellular Ca2+ (or in the presence of La3+) no secretion occurred. The extracellular Ca2+ concentration required to stimulate secretion was 10 times higher... (More)
- Gastrin and PACAP stimulate secretion of histamine and pancreastatin from isolated rat stomach ECL cells. We have examined whether or not secretion depends on the free cytosolic Ca2+ concentration ([Ca2+i) and the pathways by which gastrin and PACAP elevate [Ca2+i. Secretion was monitored by radioimmunoassay of pancreastatin and changes in [Ca2+i by video imaging. The patch clamp technique was used to record whole-cell currents and membrane capacitance (reflecting exocytosis). In the presence of 2 mM extracellular Ca2+, gastrin and PACAP induced secretion and raised [Ca2+i. Without extracellular Ca2+ (or in the presence of La3+) no secretion occurred. The extracellular Ca2+ concentration required to stimulate secretion was 10 times higher for gastrin than for PACAP. Depletion of intracellular Ca2+ pools by thapsigargin had no effect on the capacity of gastrin and PACAP to stimulate secretion. Gastrin-evoked secretion was inhibited 60-80 by L-type channel blockers and 40 by the N-type channel blocker -conotoxin GVIA. Combining L-type and N-type channel blockers did not result in greater inhibition than L-type channel blockers alone. Whole-cell patch clamp measurements confirmed that the ECL cells are equipped with voltage-dependent inward Ca2+ currents. A 500 ms depolarising pulse from -60 mV to +10 mV which maximally opened these channels resulted in an increase in membrane capacitance of 100 fF reflecting exocytosis of secretory vesicles. PACAP-evoked secretion was reduced 40 by L-type channel blockers but was not influenced by inhibition of N-type channels. SKF 96365, a blocker of both L-type and receptor-operated Ca2+ channels, inhibited PACAP-evoked secretion by 85 . Combining L-type channel blockade with SKF 96365 abolished PACAP-evoked secretion. The results indicate that gastrin- and PACAP-evoked secretion depends on Ca2+ entry and not on mobilisation of intracellular Ca2+. While gastrin stimulates secretion via voltage-dependent L-type and N-type Ca2+ channels, PACAP acts via L-type and receptor-operated Ca2+ channels. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/131229
- author
- Lindström, Erik
; Eliasson, Lena
LU
; Björkqvist, Maria
LU
and Håkanson, Rolf
LU
- organization
- publishing date
- 2001
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Journal of Physiology
- volume
- 535
- issue
- 3
- pages
- 663 - 677
- publisher
- The Physiological Society
- external identifiers
-
- wos:000171488300004
- scopus:0035884554
- ISSN
- 1469-7793
- language
- English
- LU publication?
- yes
- id
- 987dee9b-a764-434e-9af5-90dbbece3620 (old id 131229)
- alternative location
- http://jp.physoc.org/cgi/content/abstract/535/3/663
- date added to LUP
- 2016-04-01 16:46:07
- date last changed
- 2023-09-05 00:51:47
@article{987dee9b-a764-434e-9af5-90dbbece3620,
abstract = {{Gastrin and PACAP stimulate secretion of histamine and pancreastatin from isolated rat stomach ECL cells. We have examined whether or not secretion depends on the free cytosolic Ca2+ concentration ([Ca2+i) and the pathways by which gastrin and PACAP elevate [Ca2+i. Secretion was monitored by radioimmunoassay of pancreastatin and changes in [Ca2+i by video imaging. The patch clamp technique was used to record whole-cell currents and membrane capacitance (reflecting exocytosis). In the presence of 2 mM extracellular Ca2+, gastrin and PACAP induced secretion and raised [Ca2+i. Without extracellular Ca2+ (or in the presence of La3+) no secretion occurred. The extracellular Ca2+ concentration required to stimulate secretion was 10 times higher for gastrin than for PACAP. Depletion of intracellular Ca2+ pools by thapsigargin had no effect on the capacity of gastrin and PACAP to stimulate secretion. Gastrin-evoked secretion was inhibited 60-80 by L-type channel blockers and 40 by the N-type channel blocker -conotoxin GVIA. Combining L-type and N-type channel blockers did not result in greater inhibition than L-type channel blockers alone. Whole-cell patch clamp measurements confirmed that the ECL cells are equipped with voltage-dependent inward Ca2+ currents. A 500 ms depolarising pulse from -60 mV to +10 mV which maximally opened these channels resulted in an increase in membrane capacitance of 100 fF reflecting exocytosis of secretory vesicles. PACAP-evoked secretion was reduced 40 by L-type channel blockers but was not influenced by inhibition of N-type channels. SKF 96365, a blocker of both L-type and receptor-operated Ca2+ channels, inhibited PACAP-evoked secretion by 85 . Combining L-type channel blockade with SKF 96365 abolished PACAP-evoked secretion. The results indicate that gastrin- and PACAP-evoked secretion depends on Ca2+ entry and not on mobilisation of intracellular Ca2+. While gastrin stimulates secretion via voltage-dependent L-type and N-type Ca2+ channels, PACAP acts via L-type and receptor-operated Ca2+ channels.}},
author = {{Lindström, Erik and Eliasson, Lena and Björkqvist, Maria and Håkanson, Rolf}},
issn = {{1469-7793}},
language = {{eng}},
number = {{3}},
pages = {{663--677}},
publisher = {{The Physiological Society}},
series = {{Journal of Physiology}},
title = {{Gastrin and the neuropeptide PACAP evoke secretion from rat stomach histamine-containing (ECL) cells by stimulating influx of Ca2+ through different Ca2+ channels}},
url = {{https://lup.lub.lu.se/search/files/4774706/624183.pdf}},
volume = {{535}},
year = {{2001}},
}