Cited by 13Pancreatic function and diabetesIon Channels and ReceptorsCalcium signaling and nucleotide metabolism

Mechanisms of AVP‐induced glucagon release in clonal α‐cells In‐R1‐G9: involvement of Ca2+‐dependent and ‐independent pathways

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Yibchok‐anun, Sirintorn, Cheng, Henrique, Chen, Ter‐Hsin, Hsu, Walter H·2000·British Journal of Pharmacology

Abstract

The mechanisms underlying AVP‐induced increase in [Ca 2+]i and glucagon release in clonal α‐cells In‐R1‐G9 were investigated. AVP increased [Ca 2+]i and glucagon release in a concentration‐dependent manner. After the administration of AVP, glucagon was released within 30 s, quickly reached the maximum within 2 min, and maintained a steady‐state concentration for at least 15 min. In Ca 2+‐containing medium, AVP increased [Ca 2+]i in a biphasic pattern; a peak followed by a sustained plateau. In Ca 2+‐free medium, the Ca 2+ response to AVP became monophasic with lower amplitude and no plateau. Both the basal and AVP‐induced glucagon releases were lower in the absence than in the presence of extracellular Ca 2+. When [Ca 2+]i was stringently deprived by BAPTA, a Ca 2+ chelator, AVP still significantly increased glucagon release. Pretreatment with thapsigargin, a microsomal Ca 2+ ATPase inhibitor, abolished both the Ca 2+ peak and sustained plateau. AVP increased intracellular concentration of IP 3. U‐73122 (8 μ M), a phospholipase C inhibitor, abolished AVP‐induced increases in [Ca 2+]i, but only reduced AVP‐induced glucagon release by 39%. Pretreatment with nimodipine, an L‐type Ca 2+ channel blocker failed to alter AVP‐induced glucagon release or increase in [Ca 2+]i. The results suggest that AVP causes glucagon release through both Ca 2+‐dependent and ‐independent pathways. For the Ca 2+‐dependent pathway, the G q protein activates phospholipase C, which catalyzes the formation of IP 3. IP 3 induces Ca 2+ release from the endoplasmic reticulum, which, in turn, triggers Ca 2+ influx. Both Ca 2+ release and Ca 2+ influx may contribute to AVP‐induced glucagon release. British Journal of Pharmacology (2000) 129, 257–264; doi:10.1038/sj.bjp.0703037

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Authors
Yibchok‐anun, S., Cheng, H., Chen, T., & Hsu, W. H.
Affiliations
Iowa State University (US)
Venue
British Journal of Pharmacology
Publisher
Wiley
Published
2000-01
Volume
129
Issue
2
Pages
257-264
ISSN
  • 0007-1188 (ISSN-L)
  • 1476-5381
OpenAlex
W1994602202
Cited by
13
References
51
Citations by year
2020: 1 · 2017: 1 · 2016: 1 · 2015: 1 · 2013: 1 · 2012: 1
FWCI
2.16
Type
journal article
Language
en
Open access
Locations
  • British Journal of Pharmacology (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Eli Lilly and Company
  • Wayne State University
  • Iowa State University
  • National Science Council
Topics
  • Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
  • Life Sciences › Neuroscience › Sensory Systems › Ion Channels and Receptors
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Calcium signaling and nucleotide metabolism
Keywords
vasopressin, glucagon secretion, alpha cells, intracellular calcium, phospholipase C, IP3, Gq protein, thapsigargin, BAPTA, L-type calcium channels, endoplasmic reticulum calcium release, calcium influx
MeSH terms
Cyclic AMP, Amino Acid Chloromethyl Ketones, Animals, Arginine Vasopressin, Calcium, Calcium Channel Blockers, Cell Line, Clone Cells, Enzyme Inhibitors, Estrenes, Glucagon, Cricetinae, Nimodipine, Phosphodiesterase Inhibitors, Pyrrolidinones, Renal Agents, Inositol 1,4,5-Trisphosphate, Serine Proteinase Inhibitors, Thapsigargin, Calcium Channels, L-Type

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