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Query: UNIPROT:P01185 (
vasopressin
)
23,126
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
We show here that the rat
vasopressin
V(1b) receptor simultaneously activates both the G(q/11)-inositol phosphate (IP) and G(s)-cAMP pathways when transiently expressed in Chinese hamster ovary, human embryonic kidney (HEK) 293, and COS-7 cells and stimulated with
arginine-vasopressin
. Higher concentrations of the hormone, however, were needed to trigger the cAMP pathway. The nonmammalian analog arginine-vasotocin and the selective V(1b) agonist d[Cha(4)]
vasopressin
also activated the cAMP and IP pathways, although d[Cha(4)]-
vasopressin
elicited the two responses with equivalent potencies. We determined that the V(1b) receptor is present as a
homodimer
at the plasma membrane. Treatment of V(1b)-transfected HEK-293 cells with methyl-beta-cyclodextrin, a drug known to dissociate cholesterol-rich domains of the plasma membrane, shifted the EC(50) of the
vasopressin
-induced cAMP accumulation to lower concentrations and, remarkably, increased the hormone efficacy related to the activation of this second messenger system. In parallel, the
vasopressin
-mediated activation of the IP pathway was slightly reduced without modification of its EC(50). These results suggest that, as with many other G protein-coupled receptors, when transfected in heterologous cell systems, the V(1b) receptor forms dimers that signal differentially through the G(q/11) and G(s) proteins depending on the nature of the ligand as well as on its localization within specialized compartments of the plasma membrane. The present study thus illustrates how signal transduction associated with the activation of a G protein-coupled receptor can be versatile and highly dependent on both the cell context and the chemical nature of the extracellular signaling messenger.
...
PMID:Differential coupling of the vasopressin V1b receptor through compartmentalization within the plasma membrane. 1904 84
Recent studies have supported an important contribution of prorenin (PR) and its receptor (PRR) to the regulation of hypothalamic, sympathetic, and neurosecretory outflows to the cardiovascular system, including systemic release of
vasopressin
(VP), both under physiological and cardiovascular disease conditions. Still, the identification of precise cellular mechanisms and neuronal/molecular targets remain unknown. We have recently shown that PRR is expressed in VP neurons and that their activation increases neuronal activity. However, the underlying ionic channel mechanisms are undefined. Here, we performed patch-clamp electrophysiology from identified VP neurons in acute hypothalamic slices obtained from enhanced green fluorescent protein-VP transgenic rats. Voltage-clamp recordings showed that PR inhibited the magnitude of A-type K
+
current (
I
A
; ~50% at -25 mV), a subthreshold voltage-dependent current that restrains VP firing activity. PR also increased the inactivation rate of
I
A
and shifted the steady-state voltage-dependent inactivation function toward more hyperpolarized membrane potential (~7 mV shift), thus resulting in less channel availability to be activated at any given membrane potential. PR also inhibited a sustained component of
I
A
("window" current). PR-mediated changes in action potential waveform and increased firing activity were occluded when
I
A
was blocked by 4-aminopyridine. Finally, PR failed to increase superoxide production within the supraoptic nucleus/paraventricular nucleus, and PR excitatory effects persisted in slices treated with the
SOD
mimetic tempol. Taken together, these experiments indicated that PR excitatory effects on
vasopressin
neurons involve inhibition of
I
A
, due, in part, to increases in its voltage-dependent inactivation properties. Moreover, our results indicate that PR effects did not involve an increase in oxidative stress.
NEW & NOTEWORTHY
Here, we demonstrate that prorenin/the prorenin receptor is an important signaling unit for the regulation of
vasopressin
firing activity and, thus, systemic hormonal release. We identified A-type K
+
channels as key molecular targets mediating prorenin stimulation of
vasopressin
neuronal activity, thus standing as a potential therapeutic target for neurohumoral activation in cardiovascular disease.
...
PMID:A-type K
+
channels contribute to the prorenin increase of firing activity in hypothalamic vasopressin neurosecretory neurons. 2862 74
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