Angiotensin II stimulation of vascular smooth muscle cells. Secondary signalling mechanisms.
Activation of vascular smooth muscle by angiotensin II results in the phospholipase C-mediated generation of two second messengers, inositol trisphosphate (IP3) and diacylglycerol (DG). IP3 is responsible for mobilizing calcium from endoplasmic reticulum whereas DG activates protein kinase C and ultimately Na+/H+ exchange, leading to intracellular alkalinization. The IP3/calcium signal is transient, most likely serving to initiate calcium-mediated events leading to contraction, and is attenuated by activation of protein kinase C. DG formation/protein kinase C activation is sustained and may be enhanced by the concurrent intracellular alkalinization. The delay in induction of the sustained response appears to be related to cellular processing of the angiotensin II-receptor complex. Phospholipase C activity is also modulated by a cholera toxin-sensitive, pertussis toxin-insensitive guanine nucleotide regulatory protein. This guanine nucleotide regulatory protein, movement of the receptor-ligand complex, and the signals generated by the two second messengers, IP3 and DG, interact in a complex manner to cause an integrated response of vascular smooth muscle to angiotensin II stimulation.
Griendling
K K
KK
Department of Medicine, Emory University, Atlanta, GA 30322.
Tsuda
T
T
Berk
B C
BC
Alexander
R W
RW
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D004075:Diglycerides / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D015544:Inositol 1,4,5-Trisphosphate; D007295:Inositol Phosphates / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D013268:Stimulation, Chemical; D010738:Type C Phospholipases / Q000378:metabolism
D004075:Diglycerides; D007295:Inositol Phosphates; D000804:Angiotensin II; D015544:Inositol 1,4,5-Trisphosphate; D011493:Protein Kinase C; D010738:Type C Phospholipases; D002118:Calcium