Regulatory effect of experimental diabetes on the expression of endothelin receptor subtypes and their gene transcripts in the rat adrenal gland

Abstract

Endothelins (ETs) mediate paracrine control of vascular tone and secretion of steroids and catecholamines in the adrenal gland through two ET receptor subtypes, ETA and ETB. The differential distribution and function of these subtypes are responsible for the multiplicity of endothelin actions in this tissue. This study examines the regulatory effects of experimental diabetes on the gene expression, subtype specificity and localization of ET receptor subtypes, ET isopeptides, and endothelinconverting enzyme-1 (ECE-1) in the rat adrenal gland. The densities, pharmacological properties and distribution of ET receptor subtypes ETA and ETB in adrenal glands from streptozotocin-induced diabetic, insulin-treated diabetic and age-matched control rats were investigated, using radioligand receptor binding and autoradiographic techniques. The gene expression of ETA and ETB receptors ET-1, ET-3 and ECE-1 was evaluated using relative multiplex reverse transcription/PCR. The induction of diabetes caused a marked reduction in body weight but no significant change in adrenal gland size. The density of ET receptors was significantly increased in the diabetic rat adrenal gland, mainly because of an increase in the expression of ETB receptors. Insulin treatment normalized the diabetes-induced changes in the expression levels of ET receptor subtypes to control levels. The expression level of ET-1 mRNA was up-regulated, whereas ET-3 mRNA was down-regulated in the diabetic adrenal gland compared with the controls. The ECE-1 mRNA level in the adrenal gland was not altered by the induction of diabetes. Autoradiographic studies showed that ETA and ETB are the predominant receptor subtypes in the adrenal medulla and cortex respectively. These results suggest that ETA and ETB receptors are differentially distributed and regulated in the diabetic rat adrenal gland.

Endothelial Endothelin B Receptor-Mediated Prevention of Cerebrovascular Remodeling Is Attenuated in Diabetes Because of Up-Regulation of Smooth Muscle Endothelin Receptors

“…However ET B receptors, located on VSM, produce effects akin to the ET A (Schneider et al, 2007;Pollock, 2010). Mounting evidence suggests that the balance of these receptors within the vasculature may be tipped toward the contractile ET B phenotype under pathological circumstances (Ikeda et al, 2001;Stenman et al, 2002;Alabadi et al, 2004;Matsumoto et al, 2004;Ortmann et al, 2004). We have demonstrated previously that chronic blockade of the ET A receptor in type 2 diabetes decreases vascular remodeling by attenuation of MMP dysregulation .…”

“…at ASPET Journals on May 12, 2018 jpet.aspetjournals.org the diabetic rabbit urinary bladder, whereas Ikeda et al (2001) showed a significantly increased ET B gene expression in streptozotocin diabetic rat adrenal glands. Most notably, contractile ET B receptors are up-regulated in rat MCAs after focal cerebral ischemia (Henriksson et al, 2003).…”

Effect of chronic endothelin receptor antagonism on cerebrovascular function in type 2 diabetes

“…Indeed, it has been demonstrated that diabetes does upregulate vascular ET B receptor expression. Ikeda et al (23) found increased ET B receptor density in the diabetic rabbit urinary bladder, while Ortmann et al (41) showed a significantly increased ET B gene expression in STZ diabetic rat adrenal glands. In 10-wk-old NOD mice, a Type 1 diabetes model, aortic ET B gene expression was significantly increased while ET A expression was unchanged (41).…”

Downregulated FKBP12.6 expression and upregulated endothelin signaling contribute to elevated diastolic calcium and arrhythmogenesis in rat cardiomyopathy produced by l-thyroxin

“…To ensure a fixed amount of initial mRNA in parallel with GAPDH, amplification was performed using the following oligonucleotides: Sense: 5V-GCTGGGGCTCACCTGAAGG-3V, Antisense: 5V-GGATGACCTTGCCCACAGCC-3V. Specific oligonucleotide primers were used in this experiment according to the references as below: RyR2 [17], PKA [18]; ECE (endothelin-converting enzyme) [19]; PreproET-1 (prepro-endothelin-1) [20]. Density of the bands was analyzed with Labworks imaging acquisition and analysis software.…”