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- W4376095993 abstract "Signal transduction in gastric and intestinal smooth muscle is mediated by receptors coupled via distinct G proteins to various effector enzymes, including PI-specific PLC-β1 and PLC-β3, and phosphatidylcholine (PC)-specific PLC, PLD and PLA2. Activation of these enzymes is different in circular and longitudinal muscle cells, generating Ca2+-mobilizing (IP3, AA, cADPR) and other (DAG) messengers responsible for the initial and sustained phases of contraction, respectively. IP3-dependent Ca2+ release occurs only in circular muscle. Ca2+ mobilization in longitudinal muscle involves a cascade initiated by agonist-induced transient activation of PLA2 and formation of AA, AA-dependent depolarization of the plasma membrane and opening of voltage-sensitive Ca2+ channels. The influx of Ca2+ induces Ca2+ release by activating sarcoplasmic ryanodine receptor/Ca2+ channel and stimulates cADPR formation which enhances Ca2+-induced Ca2+ release. The initial [Ca2+]i transient in both muscle cell types results in Ca2+/calmodulin-dependent activation of MLC kinase, phosphorylation of MLC20 and interaction of actin and myosin. The sustained phase is mediated by a Ca2+-independent isoform of PKC, PKC-ϵ. DAG for this process is generated by PLC- and PLD-mediated hydrolysis of PC. Relaxation is mediated by cAMP- and/or cGMP-dependent protein kinase which inhibit the initial [Ca2+]i transient and reduce the sensitivity of MLC kinase to [Ca2+]i. Relaxation induced by the main enteric relaxant neurotransmitters, VIP and PACAP, involves two cascades, one of which reflects activation of adenylyl cyclase. A distinct cascade involves G-protein-dependent stimulation of Ca2+ influx leading to Ca2+/calmodulin-dependent activation of a constitutive eNOS in muscle cells; the generation of NO activates soluble guanylyl cyclase. The resultant activation of PKA and PKG is jointly responsible for muscle relaxation." @default.
- W4376095993 created "2023-05-12" @default.
- W4376095993 creator A5007881152 @default.
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- W4376095993 date "1997-05-01" @default.
- W4376095993 modified "2023-10-13" @default.
- W4376095993 title "Signal Transduction in Gastrointestinal Smooth Muscle" @default.
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- W4376095993 doi "https://doi.org/10.1016/s0898-6568(96)00180-5" @default.
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