Rho-Mancing to Sensitize Calcium Signaling for Contraction in the Vasculature: Role of Rho Kinase.

Rho-Mancing to Sensitize Calcium Signaling for Contraction in the Vasculature: Role of Rho Kinase. Adv Pharmacol. 2017;78:303-322 Authors: Szasz T, Webb RC Abstract Vascular smooth muscle contraction is an important physiological process contributing to cardiovascular homeostasis. The principal determinant of smooth muscle contraction is the intracellular free Ca(2+) concentration, and phosphorylation of myosin light chain (MLC) by activated myosin light chain kinase (MLCK) in response to increased Ca(2+) is the main pathway by which vasoconstrictor stimuli induce crossbridge cycling of myosin and actin filaments. A secondary pathway for vascular smooth muscle contraction that is not directly dependent on Ca(2+) concentration, but rather mediating Ca(2+) sensitization, is the RhoA/Rho kinase pathway. In response to contractile stimuli, the small GTPase RhoA activates its downstream effector Rho kinase which, in turn, promotes contraction via myosin light chain phosphatase (MLCP) inhibition. RhoA/Rho kinase-mediated MLCP inhibition occurs mainly by phosphorylation and inhibition of MYPT1, the regulatory subunit of MLCP, or by CPI-17-mediated inhibition of the catalytic subunit of MLCP. In this review, we describe the molecular mechanisms underlying the pivotal role exerted by Rho kinase on vascular smooth muscle contraction and discuss the main regulatory pathways for its activity. PMID: 28212799 [PubMed - in process]
Source: Advances in Pharmacology - Category: Drugs & Pharmacology Authors: Tags: Adv Pharmacol Source Type: research