Cat cerebral arterial smooth muscle cells express cytochrome P450 4A2 enzyme and produce the vasoconstrictor 20-HETE which enhances L-type Ca2+ current
Article first published online: 22 SEP 2004
The Journal of Physiology
Volume 507, Issue 3, pages 771–781, March 1998
How to Cite
Gebremedhin, D., Lange, A. R., Narayanan, J., Aebly, M. R., Jacobs, E. R. and Harder, D. R. (1998), Cat cerebral arterial smooth muscle cells express cytochrome P450 4A2 enzyme and produce the vasoconstrictor 20-HETE which enhances L-type Ca2+ current. The Journal of Physiology, 507: 771–781. doi: 10.1111/j.1469-7793.1998.771bs.x
- Issue published online: 22 SEP 2004
- Article first published online: 22 SEP 2004
- (Received 31 March 1997; accepted after revision 6 November 1997)
- 1Cerebral arteries express cytochrome P450 4A enzymes (P450 4A) and produce 20- hydroxyeicosatetraenoic acid (20-HETE), a potent constrictor of pial arterioles. It is not known which cell type in the vessel wall is responsible for the formation of 20-HETE. We examined whether freshly isolated cerebral arterial muscle cells (VSMCs) express P450 4A and produce 20-HETE. We also studied the effect of 20-HETE on pressurized cerebral arteries and on whole-cell L-type Ca2+current (ICa) recorded in cat cerebral VSMCs.
- 2Cat cerebral VSMCs incubated with [14C]arachidonic acid ([14C]AA) produced 20-HETE (3.9 ± 1.1 pmol min−1 (mg protein)−1).
- 3Reverse transcription-polymerase chain reaction studies revealed that cat cerebral VSMCs express mRNA for P450 4A which metabolizes AA to 20-HETE. Cloning and sequencing of the cDNA amplified from mRNA isolated from VSMCs showed > 96 % amino acid homology to the rat and human P450 4A2 and 4A3.
- 420-HETE (1–300 nM) induced a concentration-dependent constriction of cat cerebral arteries, which was inhibited by nifedipine.
- 5Addition of 10 and 100 nM 20-HETE to the bath increased peak ICa by 50 ± 3 and 100 ± 10 %, respectively. This effect was not influenced by altering the frequency of depolarization. 20-HETE (100 nM) failed to increase ICa in the presence of nifedipine.
- 6These results demonstrate that cat cerebral VSMCs express P450 4A enzyme, and produce 20-HETE which activates L-type Ca2+ channel current to promote cerebral vasoconstriction.