TY - JOUR
T1 - Effects of endothelin on phospholipases and generation of second messengers in cat iris sphincter and SV-CISM-2 cells
AU - Abdel-Latif, Ata A.
AU - Ding, Ke Hong
AU - Akhtar, Rashid A.
AU - Yousufzai, Sardar Y.K.
N1 - Funding Information:
This work was supported by NIH Grants R37 EY-04171, EY-04387 and EY-05738 from the U.S. Public Health Service. The authors wish to thank Dr. Zhi Ye for assistance during these studies and Ms. Ashley Skinner for typing the manuscript.
PY - 1996/9
Y1 - 1996/9
N2 - In both immortalized cat iris sphincter smooth muscle cells (SV-CISM-2 cells) and cat iris sphincter, endothelin-1 (ET-1) markedly increased the activities of phospholipase A2 (PLA2), as measured by the release of arachidonic acid (AA), phospholipase C (PLC), as measured by the production of inositol trisphosphate (IP3), and phospholipase D (PLD), as measured by the formation of phosphatidylethanol (PEt). In SV-CISM-2 cells, ET-1 induced AA release, IP3 production and PEt formation in a dose- and time-dependent manner. The dose-response studies showed that the peptide is more potent in activating PLD (EC50 = 1.2 nM) than in activating PLC (EC50 = 1.5 nM) or PLA2 (EC50 = 1.7 nM). The time course studies revealed that ET-1 activated the phospholipases in a temporal sequence in which PLA2 was stimulated first (t( 1/4 ) = 12 s), followed by PLC (t( 1/4 ) = 48 s) and lastly PLD (t( 1/4 ) = 106 s). In SV-CISM-2 cells, in contrast to the intact iris sphincter, sarafotoxin-c, an ET(B) receptor agonist, had no effect on the phospholipases, and indomethacin, a cyclooxygenase inhibitor, had no effect on the stimulatory effect of ET-1 on the phospholipases. These results suggest that in this smooth muscle cell line, ET-1 interacts with the ET(A) receptor subtype to activate, via G proteins, phospholipases A2, C and D in a temporal sequence.
AB - In both immortalized cat iris sphincter smooth muscle cells (SV-CISM-2 cells) and cat iris sphincter, endothelin-1 (ET-1) markedly increased the activities of phospholipase A2 (PLA2), as measured by the release of arachidonic acid (AA), phospholipase C (PLC), as measured by the production of inositol trisphosphate (IP3), and phospholipase D (PLD), as measured by the formation of phosphatidylethanol (PEt). In SV-CISM-2 cells, ET-1 induced AA release, IP3 production and PEt formation in a dose- and time-dependent manner. The dose-response studies showed that the peptide is more potent in activating PLD (EC50 = 1.2 nM) than in activating PLC (EC50 = 1.5 nM) or PLA2 (EC50 = 1.7 nM). The time course studies revealed that ET-1 activated the phospholipases in a temporal sequence in which PLA2 was stimulated first (t( 1/4 ) = 12 s), followed by PLC (t( 1/4 ) = 48 s) and lastly PLD (t( 1/4 ) = 106 s). In SV-CISM-2 cells, in contrast to the intact iris sphincter, sarafotoxin-c, an ET(B) receptor agonist, had no effect on the phospholipases, and indomethacin, a cyclooxygenase inhibitor, had no effect on the stimulatory effect of ET-1 on the phospholipases. These results suggest that in this smooth muscle cell line, ET-1 interacts with the ET(A) receptor subtype to activate, via G proteins, phospholipases A2, C and D in a temporal sequence.
KW - ET(A) receptor subtype
KW - SV-CSM-2 cells
KW - cat iris sphincter
KW - endothelin
KW - phospholipases A, C, D
KW - second messengers
UR - http://www.scopus.com/inward/record.url?scp=0030248911&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0030248911&partnerID=8YFLogxK
U2 - 10.1016/0929-7855(96)00520-2
DO - 10.1016/0929-7855(96)00520-2
M3 - Article
C2 - 8906557
AN - SCOPUS:0030248911
SN - 0929-7855
VL - 14
SP - 147
EP - 155
JO - Journal of Lipid Mediators and Cell Signalling
JF - Journal of Lipid Mediators and Cell Signalling
IS - 1-3
ER -