Specificity of Gq and G11 Protein Signaling in Vascular Myocytes

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Abstract

The molecular diversity of receptors and the capability of these receptors to activate multiple types of G proteins theoretically allow the transmission of signals through multiple effector pathways. In functional experiments, however, the number of possibilities may be strongly reduced. We have recently reported that in vascular myocytes, α1-adrenoceptors activate two G proteins composed of αq13 and α1132 subunits, leading to increase in cytoplasmic [Ca2+]i concentration. Only the αq subunit transduces the signal to a phospholipase C-β, which hydrolyzes phosphatidylinositol 4,5-bisphosphate to generate inositol 1,4,5-trisphosphate and the subsequent release of Ca2+ from the intracellular store. In contrast, the α11 subunit activates Ca2+ entry through a nonspecific cation channel in the presence of increased [Ca2+]i level. These coupling mechanisms reveal the distinct participation of Gq and G11 in the regulation of vascular contractility. Specific Gq- or G11-activated pathways should be taken into account to understand the various contraction profiles induced by different vasoconstrictors.

Section snippets

• Gq/G11-Activated Transduction Pathways

Receptor activation of pertussis toxin-insensitive phospholipase C activity is generally transduced by members of the Gq protein family. This family consists of five members, designated Gq, G11, G14, G16, and G15, the murine counterpart of G16 (Simon et al. 1991). Evidence suggests that the α subunits of all of these G proteins have the potential to activate phospholipase C activity (Hepler et al. 1993). Wu et al. (1992)showed that transfection of cDNAs coding for Gq and G11 into COS-7 cells

• Gq-Activated Ca2+ Release

The heterotrimeric G proteins involved in Ca2+ release from the intracellular store have been identified in the rat leukemia cell line (RBL-2H3-hm1) and vascular myocytes in response to activation of muscarinic M1 or α1-adrenergic receptors (Dippel et al. 1996, Macrez-Lepretre et al. 1997b). So far, the only method that allows discrimination between Gq and G11 and between the different β and γ subunits is the nuclear microinjection of antisense oligonucleotides for selective and transient

• G11-Activated Ca2+ Entry

In vascular myocytes, the α1-adrenoceptor-induced rise in [Ca2+]i involves both Gq and G11 proteins. This increase in [Ca2+]i results from intracellular Ca2+ release (via Gq) and Ca2+ entry. It has been reported that depletion of the intracellular Ca2+ store may promote a sustained Ca2+ entry through dihydropyridine-resistant Ca2+ channels, but the mechanisms have not been definitively identified (Clapham 1995, Favre et al. 1996). In vascular myocytes, a part of the norepinephrine-induced Ca2+

• Concluding Remarks

The distinct functions of Gq and G11 in vascular myocytes are summarized in Fig. 3. The Gαq13 protein activated by the α1-adrenoceptor releases the αq subunit, which stimulates a PLC-β. Hydrolysis of PIP2 leads to generation of IP3, which activates the IP3-gated channels of the sarcoplasmic reticulum and induces Ca2+ release from the intracellular store.

Diacylglycerol, the physiological activator of protein kinase C, may lead to phosphorylation of L-type Ca2+ channels and increase in Ca2+

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