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大鼠中血管加压素抗利尿活性的性别差异。

Sex difference in the antidiuretic activity of vasopressin in the rat.

作者信息

Wang Y X, Edwards R M, Nambi P, Stack E J, Pullen M, Share L, Crofton J T, Brooks D P

机构信息

Department of Renal Pharmacology, SmithKline Beecham Pharmaceuticals, King of Prussia, Pennsylvania 19406-0939.

出版信息

Am J Physiol. 1993 Dec;265(6 Pt 2):R1284-90. doi: 10.1152/ajpregu.1993.265.6.R1284.

Abstract

A possible gender difference in the antidiuretic activity of vasopressin was studied in male and female Sprague-Dawley rats. Infusion of vasopressin (3-100 pg.kg-1.min) into conscious, chronically instrumented water-loaded rats resulted in a dose-dependent antidiuresis in both male and female rats. Male rats, however, were more than three times more sensitive to vasopressin than female rats. Thus the effective doses of vasopressin (pg.kg-1.min-1) to decrease urine flow to 30 microliters.min-1.100 g-1 (18 +/- 5 in males; 58 +/- 12 in females), to increase urine osmolality to 600 mosmol/kgH2O (35 +/- 5 in males; 119 +/- 15 in females), and to decrease free water clearance to 30 microliters.min-1.100 g-1 (8 +/- 3 in males; 28 +/- 7 in females) were significantly (P < 0.05) lower in males. Furthermore, in vitro studies in papillary collecting duct cells demonstrated a significantly higher density of vasopressin V2 receptors and a greater ability of vasopressin to stimulate adenosine 3',5'-cyclic monophosphate (cAMP) accumulation in males than in females. Vasopressin V2-receptor density (maximum binding) was 359 +/- 47 and 238 +/- 22 fmol/mg in male and female rats, respectively (P < 0.05). There was no difference in apparent dissociation constants (Kd). Vasopressin resulted in a dose-dependent increase in cAMP accumulation in papillary collecting duct cells, and at the highest concentration of vasopressin used (10(-8) M) cAMP increased from 44 +/- 10 to 182 +/- 51 fmol/micrograms protein in males and from 30 +/- 4 to 91 +/- 18 fmol/micrograms protein in females (P < 0.05). (ABSTRACT TRUNCATED AT 250 WORDS)

摘要

在雄性和雌性斯普拉格 - 道利大鼠中研究了血管加压素抗利尿活性可能存在的性别差异。向有意识的、长期植入仪器的水负荷大鼠输注血管加压素(3 - 100 pg·kg⁻¹·min),在雄性和雌性大鼠中均导致剂量依赖性的抗利尿作用。然而,雄性大鼠对血管加压素的敏感性是雌性大鼠的三倍多。因此,使尿流降至30微升·min⁻¹·100 g⁻¹(雄性为18±5;雌性为58±12)、使尿渗透压升至600 mosmol/kgH₂O(雄性为35±5;雌性为119±15)以及使自由水清除率降至30微升·min⁻¹·100 g⁻¹(雄性为8±3;雌性为28±7)时,血管加压素的有效剂量(pg·kg⁻¹·min⁻¹)在雄性中显著更低(P < 0.05)。此外,对乳头集合管细胞的体外研究表明,雄性血管加压素V2受体密度显著高于雌性,且血管加压素刺激雄性腺苷3',5'-环磷酸(cAMP)积累的能力也更强。雄性和雌性大鼠血管加压素V2受体密度(最大结合量)分别为359±47和238±22 fmol/mg(P < 0.05)。表观解离常数(Kd)无差异。血管加压素导致乳头集合管细胞中cAMP积累呈剂量依赖性增加,在所用血管加压素的最高浓度(10⁻⁸ M)时,雄性cAMP从44±10增加至182±51 fmol/μg蛋白质,雌性从30±4增加至91±18 fmol/μg蛋白质(P < 0.05)。(摘要截断于250字)

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