Your browser doesn't support javascript.
loading
Phosphodiesterases Mediate the Augmentation of Myogenic Constriction by Inhibitory G Protein Signaling and is Negatively Modulated by the Dual Action of RGS2 and 5.
Sun, Bo; Smith, Nia; Dixon, Alethia J; Osei-Owusu, Patrick.
Afiliación
  • Sun B; Department of Physiology and Biophysics, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA.
  • Smith N; Department of Physiology and Biophysics, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA.
  • Dixon AJ; Department of Physiology and Biophysics, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA.
  • Osei-Owusu P; Department of Physiology and Biophysics, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA.
Function (Oxf) ; 5(2): zqae003, 2024.
Article en En | MEDLINE | ID: mdl-38486977
ABSTRACT
G protein regulation by regulators of G protein signaling (RGS) proteins play a key role in vascular tone maintenance. The loss of Gi/o and Gq/11 regulation by RGS2 and RGS5 in non-pregnant mice is implicated in augmented vascular tone and decreased uterine blood flow (UBF). RGS2 and 5 are closely related and co-expressed in uterine arteries (UA). However, whether and how RGS2 and 5 coordinate their regulatory activities to finetune G protein signaling and regulate vascular tone are unclear. Here, we determined how the integrated activity of RGS2 and 5 modulates vascular tone to promote UBF. Using ultrasonography and pressure myography, we examined uterine hemodynamics and myogenic tone (MT) of UA of wild type (WT), Rgs2-/-, Rgs5-/-, and Rgs2/5 dbKO mice. We found that MT was reduced in Rgs5-/- relative to WT or Rgs2-/- UA. Activating Gi/o with dopamine increased, whereas exogenous cAMP decreased MT in Rgs5-/- UA to levels in WT UA. Dual deletion of Rgs2 and 5 abolished the reduced MT due to the absence of Rgs5 and enhanced dopamine-induced Gi/o effects in Rgs2/5 dbKO UA. Conversely, and as in WT UA, Gi/o inhibition with pertussis toxin or exogenous cAMP decreased MT in Rgs2/5 dbKO to levels in Rgs5-/- UA. Inhibition of phosphodiesterases (PDE) concentration-dependently decreased and normalized MT in all genotypes, and blocked dopamine-induced MT augmentation in Rgs2-/-, Rgs5-/-, and Rgs2/5 dbKO UA. We conclude that Gi/o augments UA MT in the absence of RGS2 by a novel mechanism involving PDE-mediated inhibition of cAMP-dependent vasodilatation..
Asunto(s)
Palabras clave
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Transducción de Señal / Dopamina Límite: Animals Idioma: En Revista: Function (Oxf) Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Transducción de Señal / Dopamina Límite: Animals Idioma: En Revista: Function (Oxf) Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido