Impaired arginine–vasopressin-induced aldosterone release from adrenal gland cells in mice lacking the vasopressin V1A receptor

doi:10.1016/j.ejphar.2007.03.022

European Journal of Pharmacology

Volume 566, Issues 1–3, 2 July 2007, Pages 226-230

https://doi.org/10.1016/j.ejphar.2007.03.022 Get rights and content

Abstract

We examined aldosterone release in response to stimulation with arginine–vasopressin (AVP) using adrenal gland cells. AVP caused a significant increase in aldosterone release from the dispersed adrenal gland cells of wild-type mice (V_1AR^+/+) at concentrations from 0.1 μM to 1 μM. In contrast, AVP-induced aldosterone release was impaired in adrenal gland cells from mice lacking the vasopressin V_1A receptor (V_1AR^−/−), while adrenocorticotropic hormone (ACTH)-induced aldosterone release in V_1AR^−/− mice was not significantly different from that in V_1AR^+/+ mice. In addition, a vasopressin V_1A receptor-selective antagonist 1-[1-[4-(3-acetylaminopropoxy)benzoyl]-4-piperidyl]-3,4-dihydro-2(1H)-quinolinone (OPC-21268) potently inhibited AVP-induced aldosterone release. Thus, our study clearly demonstrates that AVP-induced aldosterone release from adrenal gland cells is mediated via the vasopressin V_1A receptor in mice.

Introduction

The neurohypophyseal peptide, arginine–vasopressin (AVP), plays a major role in regulating water excretion by the kidney. It also participates in other physiological functions such as vasoconstriction and glycogenolysis through vasopressin receptors, which are divided into at least three types: vasopressin V_1A, V_1B, and V₂ receptors (Thibonnier et al., 2002). The vasopressin V_1A receptor, which mainly mediates blood pressure control, is expressed in the liver, brain, heart, kidney, spleen, uterus, and adrenal glands, as well as in vessels. The vasopressin V_1A receptor also mediates mineralocorticoid (aldosterone) secretion from zona glomerulosa cells in the human adrenal cortex (Guillon et al., 1995). Pharmacological studies have shown that the application of a non-specific vasopressin V₁ receptor antagonist (Des-Gly-(Pha¹, d-Try(Et)², Lys⁶, Arg⁸)-AVP) inhibited AVP-induced aldosterone release from the rat adrenal cortex (Mazzocchi et al., 1993). These findings suggest that AVP plays a crucial role in stimulating aldosterone release via the vasopressin V_1A receptor in human and rat adrenal glands. Recently, we successfully generated a mouse lacking the vasopressin V_1A receptor (V_1AR^−/−) (Koshimizu et al., 2006, Egashira et al., 2004). V_1AR^−/− mice are not lethal and have no apparent anatomical anomaly in organs, including the heart, brain, liver, muscle, and kidney. In our previous study, we observed a decrease in the corticosterone response to ACTH in mutant mice (Koshimizu et al., 2006). In the present study, we investigated the functional role of AVP, in addition to that of a V_1A selective antagonist, 1-[1-[4-(3-acetylaminopropoxy)benzoyl]-4-piperidyl]-3,4-dihydro-2(1H)-quinolinone (OPC-21268), on aldosterone secretion from mouse adrenal glands with vasopressin V_1A receptor-deficient mice (V_1AR^−/−).

Section snippets

Animals

The generation of vasopressin V_1A receptor-deficient (V_1AR^−/−) mice was previously described (Egashira et al., 2004, Koshimizu et al., 2006). Briefly, by homologous recombination, we disrupted exon 1, which contains the translation initiation codon. Non-vasopressin V_1A receptor-deficient littermates (V_1AR^+/+) were used as age-matched control subjects for V_1AR^−/− mice. Animals were housed in micro-isolator cages in a pathogen-free barrier facility. V_1AR^+/+ and V_1AR^−/− mice were placed on a 12-h

Expression of vasopressin receptors in the mouse adrenal glands

To determine whether vasopressin receptors are involved in the response of aldosterone release to AVP, RT-PCR was used to assess the expression of the AVP receptor subtypes and the OT receptor in adrenal gland tissues from male V_1AR^+/+ and V_1AR^−/− mice. As shown in Fig. 1, vasopressin V_1A receptor mRNA was detected in the adrenal gland tissues from V_1AR^+/+ mice but not from V_1AR^−/− mice. Vasopressin V_1B, V₂, and OT receptor mRNAs were also detected in the adrenal gland tissues from both V_1AR^+/+

Discussion

Our analysis of AVP receptor expression in the adrenal gland indicates that the vasopressin V_1A receptor is predominantly expressed in the cortex rather than in the medulla. This finding for the mouse adrenal gland is in good agreement with previous studies of the human and rat adrenal glands (Grazzini et al., 1999, Grazzini et al., 1996, Guillon et al., 1995, Mazzocchi et al., 1993). In human and rat, AVP is reported to stimulate aldosterone secretion via activation of the vasopressin V_1A

Acknowledgements

We thank Dr. C. Serradeil for providing SSR149415 and Dr. T. Mori for providing OPC-21268. This work was supported by research grants from The Japan Health Sciences, the Novartis Foundation, and the Takeda Science Foundation.

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Impaired arginine–vasopressin-induced aldosterone release from adrenal gland cells in mice lacking the vasopressin V1A receptor

Abstract

Introduction

Section snippets

Animals

Expression of vasopressin receptors in the mouse adrenal glands

Discussion

Acknowledgements

Neurosci. Lett.

J. Steroid Biochem. Mol. Biol.

Prog. Brain Res.

In vivo and in vitro screening for illegitimate receptors in adrenocorticotropin-independent macronodular adrenal hyperplasia causing Cussing's syndrome: identification of two causes of gonadotropin/gastric inhibitory polypeptide-dependent hypercortisolism

J. Clin. Endocrinol. Metab.

Agonist-stimulated turnover of the phosphoinositides and the regulation of adrenocortical steroidogenesis

J. Mol. Endocrinol.

The effects of proopiomelanocortin deficiency on murine adrenal development and responsiveness to adrenocorticotropin

Endocrinology

In vivo and in vitro effects of AVP and V1A receptor antagonist on Cushing's syndrome due to ACTH-independent bilateral macronodular adrenocortical hyperplasia

Clin. Endocrinol. (Oxf)

Impaired arginine–vasopressin-induced aldosterone release from adrenal gland cells in mice lacking the vasopressin V_1A receptor