Cited by 23Phosphodiesterase function and regulationCalcium signaling and nucleotide metabolismIon channel regulation and function

Inhibition of extracellular Ca 2+ entry by YC-1, an activator of soluble guanylyl cyclase, through a cyclic GMP-independent pathway in rat neutrophils 1 1Abbreviations: CO, carbon monoxide; CPA, cyclopiazonic acid; fMLP, formyl-methionyl-leucyl-phenylalanine; HBSS, Hanks’ balanced salt solution; IP3, inositol 1,4,5-trisphosphate; NO, nitric oxide; PKC, protein kinase C; PKG, cyclic GMP-dependent protein kinase; PLC, phospholipase C; PMA, phorbol 12-myristate 13-acetate; Rp-8-pCPT-cGMPS, 8-(4-chlorophenylthio)guanosine-3′,5′-monophosphorothioate, Rp-isomer; sGC, soluble guanylyl cyclase; and SNP, sodium nitroprusside.

Wang, Jih-Pyang, Chang, Ling-Chu, Huang, Li-Jiau, Kuo, Sheng-Chu·2001·Biochemical Pharmacology

Abstract

The effects of a soluble guanylyl cyclase (sGC) activator, 3-(5'-hydroxymethyl-2'-furyl)-1-benzyl indazole (YC-1), on formyl-methionyl-leucyl-phenylalanine (fMLP)-stimulated [Ca(2+)](i) elevation in rat neutrophils were examined. YC-1 produced a concentration-dependent inhibition of [Ca(2+)](i) elevation. Pretreatment of neutrophils with YC-1 did not enhance its inhibitory effect. YC-1 also inhibited the [Ca(2+)](i) changes caused by ionomycin. In a biphasic model, measuring the [Ca(2+)](i) stimulation by fMLP in a Ca(2+)-free medium followed by reintroduction of Ca(2+), YC-1 mainly affected Ca(2+) influx. YC-1 also inhibited active and passive Mn(2+) influx, and this inhibitory effect was not attenuated by the sGC inhibitor 6-anilino-5,8-quinolinequinone (LY83583). Sodium nitroprusside did not affect the fMLP-stimulated [Ca(2+)](i) changes. Pretreatment of neutrophils with the cyclic GMP-dependent protein kinase inhibitor 8-(4-chlorophenylthio) guanosine-3',5'-monophosphorothioate, Rp-isomer (Rp-8-pCPT-cGMPS), LY83583, the protein phosphatase 2B inhibitor cyclosporin A, or the protein kinase inhibitor staurosporine did not attenuate the inhibition of [Ca(2+)](i) by YC-1. YC-1 inhibited the fMLP-stimulated protein tyrosine phosphorylation. These results indicate that cyclic GMP does not play an important role in the regulation of [Ca(2+)](i) in rat neutrophils. Inhibition of fMLP-stimulated [Ca(2+)](i) changes by YC-1 is mainly via the blockade of Ca(2+) entry through the inhibition of tyrosine kinase activity, but not the stimulation of protein kinase C and protein phosphatase 2B.

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Crossref · 10.1016/s0006-2952(01)00725-0

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Authors
Wang, J.-P., Chang, L.-C., Huang, L.-J., & Kuo, S.-C.
Affiliations
  • China Medical University (TW)
  • Taichung Veterans General Hospital (TW)
Corresponding author
Wang, Jih-Pyang
Venue
Biochemical Pharmacology
Publisher
Elsevier BV
Published
2001-09
Volume
62
Issue
6
Pages
679-684
ISSN
0006-2952 (ISSN-L)
OpenAlex
W1983898467
Cited by
23
References
42
Citations by year
2018: 1 · 2012: 1
FWCI
1.05
Type
journal article
Language
en
Open access
closed
Locations
  • Biochemical Pharmacology (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Science Council
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Phosphodiesterase function and regulation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Calcium signaling and nucleotide metabolism
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
Keywords
YC-1, soluble guanylate cyclase, extracellular calcium influx, neutrophils, fMLP, intracellular calcium, LY83583, ionomycin, manganese influx, chemotaxis, chemokine signaling, phospholipase C
MeSH terms
Animals, Calcium, Enzyme Activation, Cyclic GMP, Guanylate Cyclase, Indazoles, Manganese, Neutrophils, Phosphorylation, Platelet Aggregation Inhibitors, Solubility, Tyrosine, Ion Transport, Rats, In Vitro Techniques

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