Increased potency of α1-adrenergic receptors to induce inositol phosphates production correlates with the up-regulation of α1d/Ghα/phospholipase Cδ1 signaling pathway in term rat myometrium

Dec 27, 2007Reproduction (Cambridge, England)

Stronger alpha 1-adrenergic receptor signaling linked to increased activity in a specific cell communication pathway in late-term rat uterus muscle

AI simplified

Circadian Biology on OpenScience ↗PubMed ↗DOI ↗

Abstract

An increased level of alpha1-adrenergic receptor/Gh alpha protein coupling and PLC delta 1 at term was observed, with increases of 147% and 65%, respectively, compared to mid-pregnancy.

The alpha1-adrenergic receptor signaling pathway is up-regulated in rat myometrium at term.
A 70% increase in the expression of the alpha1d-adrenergic receptor subtype was noted at term.
Phenylephrine, an alpha1-agonist, enhanced inositol phosphate production at term, with a tenfold increase in potency compared to mid-pregnancy.
Uterine muscle contraction in response to phenylephrine did not show increased potency at term despite enhanced inositol phosphate production.
Norepinephrine exhibited similar effects on inositol phosphate production and contraction as phenylephrine.
The findings suggest that the alpha1-adrenergic receptor pathway may be involved in myometrial cell proliferation or hypertrophy rather than labor initiation.

AI simplified

In the present study, we studied the potential regulation by rat myometrial alpha1-adrenergic receptors (alpha1-AR) of the newly identified Gh alpha protein/phospholipase C delta 1 (PLC delta 1) signaling pathway and compared myometrial inositol phosphates (InsP) production and activity of the uterine circular muscle in response to alpha1-AR activation between mid-pregnancy and term. For this, we quantified the level of rat myometrial alpha1-AR coupling to Gh alpha protein by photoaffinity-labeling, the cytosolic amount of PLC delta 1 enzyme by immunoblotting, and the expression level of alpha1-AR subtypes by RT-PCR. The results showed an increased level of alpha1-AR/Gh alpha protein coupling and the amount of PLC delta 1 at term (+147 and +65% respectively, versus mid-pregnancy). This was correlated with an up-regulation of alpha 1d-AR subtype (+70% versus mid-pregnancy). Incubation of myometrial strips with phenylephrine (Phe), a global alpha1-agonist, increased InsP production in a dose-dependent manner at both mid-pregnancy and term, but with an enhanced potency (tenfold decrease in EC(50) value) at term. Phe also dose-dependently induced contraction of the circular muscle at both mid-pregnancy and term. However, unlike InsP response, no amelioration of potency was observed at term. Similar results were obtained with the endogenous agonist norepinephrine. Our results show, for the first time, that rat myometrial alpha 1d-AR/Gh alpha/PLC delta 1 signaling pathway is up-regulated at term. This is associated with an increased potency of alpha1-AR to elicit InsP production but not uterine contraction at this period. It is thus hypothesized that alpha1-AR, through activation of Gh alpha/PLC delta 1 system, are not primarily involved in the initiation of labor but may rather regulate responses such as myometrial cell proliferation or hypertrophy.

Full Text

Full text is available at the source.

View full text (HTML) ↗View full text (PDF) ↗View full text ↗

Increased potency of α1-adrenergic receptors to induce inositol phosphates production correlates with the up-regulation of α1d/Ghα/phospholipase Cδ1 signaling pathway in term rat myometrium

Abstract

Full Text

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the circadian biology brief

Abstract

Full Text

Related papers

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the circadian biology brief