Involvement of phospholipase C in endothelin 1-induced stimulation of Ca++ channels and basilar artery contraction in rabbits.
Endothelin 1 (ET-1) is a major cause of cerebral vasospasm after subarachnoid hemorrhage (SAH), and extracellular Cal++ influx plays an essential role in ET-1-induced vasospasm. The authors recently demonstrated that ET-1 activates two types of Ca"-permeable nonselective cation channels (designated NSCC-1 and NSCC-2) and a store-operated Cal++ channel (SOCC) in vascular smooth-muscle cells located in the basilar arteries (BAs) of rabbits. In the present study, they investigate the effects of phospholipase C (PLC) on ET-1-induced activation of these Ca++ channels and BA contraction by using the PLC inhibitor U73122. Methods. To determine which Cal++ channels are activated via a PLC-dependent pathway, these investigators monitored the intracellular free Cal++ concentration ([Ca++]i). The role of PLC in ET-1-induced vascular contraction was examined by performing a tension study of rabbit BA rings. The U73122 inhibited the ET-1-induced transient increase in [Ca++]i, which resulted from mobilization of Ca++ from the intracellular store. Phospholipase C also inhibited ET-1-induced extracellular Ca++ influx through the SOCC and NSCC-2, but not through the NSCC-1. The U73122 inhibited the ET-1-induced contraction of the rabbit BA rings, which depended on extracellular Cal++ influx through the SOCC and NSCC-2. Conclusions. These results indicate the following. (1) The SOCC and NSCC-2 are stimulated by ET-1 via a PLC-dependent cascade whereas NSCC-1 is stimulated via a PLC-independent cascade. (2) The PLC is involved in the ET-1-induced contraction of rabbit BA rings, which depends on extracellular Ca++ influx through the SOCC and NSCC-2.
Kawanabe
Yoshifumi
Y
Department of Neurosurgery, Kyoto University Graduate School of Medicine, Kyoto, Japan. kawanabe@takatsuki.jrc.or.jp
Masaki
Tomoh
T
Hashimoto
Nobuo
N
D000818:Animals; D001488:Basilar Artery / Q000503:physiopathology; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000502:physiology*; D020864:Calcium Channels, N-Type / Q000502:physiology; D019332:Endothelin-1 / Q000502:physiology*; D066298:In Vitro Techniques; D007295:Inositol Phosphates / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000503:physiopathology*; D011817:Rabbits; D010738:Type C Phospholipases / Q000502:physiology*; D014661:Vasoconstriction / Q000502:physiology*; D020301:Vasospasm, Intracranial / Q000503:physiopathology*
D015220:Calcium Channels; D020864:Calcium Channels, N-Type; D019332:Endothelin-1; D007295:Inositol Phosphates; D010738:Type C Phospholipases; D002118:Calcium