title: Secondary signalling mechanisms in angiotensin II-stimulated vascular smooth muscle cells.
abstract: 1. Activation of vascular smooth muscle by angiotensin II results in the generation of two second messengers, inositol trisphosphate (IP3) and diacylglycerol (DG). 2. IP3 is responsible for mobilizing calcium from endoplasmic reticulum. This signal is transient, most likely serving to initiate calcium events leading to contraction, and is attenuated by activation of protein kinase C. 3. DG stimulates protein kinase C and ultimately Na+/H+ exchange, leading to intracellular alkalinization. Accumulation of DG/activation of protein kinase C is sustained, and may be enhanced by concurrent intracellular alkalinization. The delay in induction of the sustained response appears to be related to cellular processing of the angiotensin II-receptor complex. 4. Angiotensin II-stimulated, phospholipase C-mediated IP3 formation is also modulated by a pertussis toxin-insensitive guanine nucleotide regulatory protein. 5. The GTP binding 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 cells to angiotensin II stimulation.
authors.affiliation: Department of Medicine, Harvard Medical School, Boston, Massachusetts.
authors.forename: K K
authors.initials: KK
authors.lastname: Griendling
authors.forename: B C
authors.initials: BC
authors.lastname: Berk
authors.forename: L
authors.initials: L
authors.lastname: Socorro
authors.forename: T
authors.initials: T
authors.lastname: Tsuda
authors.forename: P
authors.initials: P
authors.lastname: Delafontaine
authors.forename: R W
authors.initials: RW
authors.lastname: Alexander
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D006801:Humans; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D000804:Angiotensin II