کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2007164 1066365 2008 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
[Orn5]URP acts as a pure antagonist of urotensinergic receptors in rat cortical astrocytes
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
[Orn5]URP acts as a pure antagonist of urotensinergic receptors in rat cortical astrocytes
چکیده انگلیسی

Cultured rat astrocytes, which express functional urotensin II (UII)/UII-related peptide (URP) receptors (UT), represent a very suitable model to investigate the pharmacological profile of UII and URP analogs towards native UT. We have recently designed three URP analogs [d-Trp4]URP, [Orn5]URP and [d-Tyr6]URP, that act as UT antagonists in the rat aortic ring bioassay. However, it has been previously reported that UII/URP analogs capable of inhibiting the contractile activity of UII possess agonistic activity on UT-transfected cells. In the present study, we have compared the ability of URP analogs to compete for [125I]URP binding and to modulate cytosolic calcium concentration ([Ca2+]c) in cultured rat astrocytes. All three analogs displaced radioligand binding: [d-Trp4]URP and [d-Tyr6]URP interacted with high- and low-affinity sites whereas [Orn5]URP only bound high-affinity sites. [d-Trp4]URP and [d-Tyr6]URP both induced a robust increase in [Ca2+]c in astrocytes while [Orn5]URP was totally devoid of activity. [Orn5]URP provoked a concentration-dependent inhibition of URP- and UII-evoked [Ca2+]c increase and a rightward shift of the URP and UII dose–response curves. The present data indicate that [d-Trp4]URP and [d-Tyr6]URP, which act as UII antagonists in the rat aortic ring assay, behave as agonists in the [Ca2+]c mobilization assay in cultured astrocytes, whereas [Orn5]URP is a pure selective antagonist in both rat aortic ring contraction and astrocyte [Ca2+]c mobilization assays.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Peptides - Volume 29, Issue 5, May 2008, Pages 813–819
نویسندگان
, , , , , , , , ,