Biochemical and functional characterization of high‐affinity urotensin II receptors in rat cortical astrocytes

Abstract

The urotensin II (UII) gene is primarily expressed in the central nervous system, but the functions of UII in the brain remain elusive. Here, we show that cultured rat astrocytes constitutively express the UII receptor (UT incorporation and increased intracellular Ca 2+ concentration in a dose-dependent manner. The stimulatory effect of rUII on polyphosphoinositide turnover was abolished by the phospholipase C inhibitor U73122, but only reduced by 56% by pertussis toxin. The GTP analogue Gpp(NH)p caused its own biphasic displacement of [ 125 I]rUII binding and provoked an affinity shift of the competition curve of rUII. Pertussis toxin shifted the competition curve towards a single lower affinity state. Taken together, these data demonstrate that rat astrocytes express high-and low-affinity UII binding sites coupled to G proteins, the high-affinity receptor exhibiting the same pharmacological and functional characteristics as UT.

International Union of Basic and Clinical Pharmacology. XCII. Urotensin II, Urotensin II–Related Peptide, and Their Receptor: From Structure to Function

“…9A). The involvement of PLC in UT signaling has been confirmed in cultured rat cortical astrocytes (Castel et al, 2006;Jarry et al, 2010). IP 3 binds to the IP 3 receptor, a calcium channel on the membrane of the endoplasmic reticulum, resulting in an increase in cytoplasmic calcium levels (Parys and de Smedt, 2012) (Fig.…”

“…Expression of UII mRNA occurs in neurons (Jégou et al, 2006), astrocytes (Castel et al, 2006;Desrues et al, 2012), and endothelial cells .…”

Transcriptional profiling of the megabladder mouse: A unique model of bladder dysmorphogenesis

“…Such studies suggest that both ligand and GTP concentration as well as desensitization all play an important role in regulating the ratio of receptor coupling to functionally distinct G-proteins, thereby modulating the precise biological response elicited. In addition, prior studies indicate that cultured rat astrocytes constitutively express both low-affinity and high-affinity GPR14 receptors (Castel et al, 2006). It is plausible that bladder smooth muscle cells also express both low-and high-affinity GPR14 receptors, and that the dose-dependent binding of Urp to these distinct receptor subtypes results in the biphasic regulation of SRF expression in cultured smooth muscle cells.…”

State-dependent calcium mobilization by urotensin-II in cultured human endothelial cells

“…For example, the effect of U-II was abolished by thapsigargin, indicating the participation of endoplasmic reticulum Ca 2+ pools in rhabdomyosarcoma cell line [27] as well as in frog motor nerve terminals [12]. In rat, rabbit and cat blood vessels [2,32,55,56,61] and in rat cultured astrocytes [16], the effect of U-II was inhibited by the phospholipase C inhibitor U-73122, indicating the involvement of phospholipase-C/IP 3 pathways. In contrast, U-II elevated [Ca 2+ ] i largely by facilitating Ca 2+ entry through plasmalemmal Ca 2+ channels in rat spinal motoneurons [30].…”