PMID- 11551512
OWN - NLM
STAT- MEDLINE
DCOM- 20010920
LR  - 20190623
IS  - 0006-2952 (Print)
IS  - 0006-2952 (Linking)
VI  - 62
IP  - 6
DP  - 2001 Sep 15
TI  - Inhibition of extracellular Ca(2+) entry by YC-1, an activator of soluble 
      guanylyl cyclase, through a cyclic GMP-independent pathway in rat neutrophils.
PG  - 679-84
AB  - 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.
FAU - Wang, J P
AU  - Wang JP
AD  - Department of Education and Research, Taichung Veterans General Hospital, 407, 
      ROC, Taichung, Taiwan. w1994@vghtc.gov.tw
FAU - Chang, L C
AU  - Chang LC
FAU - Huang, L J
AU  - Huang LJ
FAU - Kuo, S C
AU  - Kuo SC
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Biochem Pharmacol
JT  - Biochemical pharmacology
JID - 0101032
RN  - 0 (Indazoles)
RN  - 0 (Platelet Aggregation Inhibitors)
RN  - 154453-18-6 (3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole)
RN  - 42HK56048U (Tyrosine)
RN  - 42Z2K6ZL8P (Manganese)
RN  - EC 4.6.1.2 (Guanylate Cyclase)
RN  - H2D2X058MU (Cyclic GMP)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Animals
MH  - Calcium/*metabolism
MH  - Cyclic GMP/*metabolism
MH  - Enzyme Activation
MH  - Guanylate Cyclase/*metabolism
MH  - In Vitro Techniques
MH  - Indazoles/*pharmacology
MH  - Ion Transport
MH  - Manganese/metabolism
MH  - Neutrophils/*drug effects/enzymology/metabolism
MH  - Phosphorylation
MH  - Platelet Aggregation Inhibitors/*pharmacology
MH  - Rats
MH  - Solubility
MH  - Tyrosine/metabolism
EDAT- 2001/09/12 10:00
MHDA- 2001/09/21 10:01
CRDT- 2001/09/12 10:00
PHST- 2001/09/12 10:00 [pubmed]
PHST- 2001/09/21 10:01 [medline]
PHST- 2001/09/12 10:00 [entrez]
AID - S0006-2952(01)00725-0 [pii]
AID - 10.1016/s0006-2952(01)00725-0 [doi]
PST - ppublish
SO  - Biochem Pharmacol. 2001 Sep 15;62(6):679-84. doi: 10.1016/s0006-2952(01)00725-0.