Sains Malaysiana 50(2)(2021): 481-492

http://dx.doi.org/10.17576/jsm-2021-5002-19

The Effects of Acute Glucoprivation on Adrenomedullary Function in SHR and WKY Rats

(Kesan Deprivasi Glukosa Akut pada Fungsi Medula Adrenal pada Tikus SHR dan WKY)

HANAFI AHMAD DAMANHURI¹*, PETER ROBERT DUNKLEY² & ANN KATHLEEN GOODCHILD³

¹Department of Biochemistry, Faculty of Medicine, Universiti Kebangsaan Malaysia Medical Centre, Jalan Yaacob Latif, Bandar Tun Razak, 56000 Kuala Lumpur, Federal Territory, Malaysia

²School of Biomedical Sciences and Pharmacy, The University of Newcastle, Callaghan, New South Wales, 2308, Australia

³Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Macquarie University, Sydney, New South Wales 2109, Australia

Received: 11 March 2020/Accepted: 17 July 2020

ABSTRACT

We have shown previously, acute intraperitoneal administration of 2-deoxy-d-glucose (2DG) into Sprague-Dawley rats led to activation of the adrenal medulla chromaffin cells, indicated with increased protein kinase activity and increased tyrosine hydroxylase (TH) phosphorylation, as well as increased plasma adrenaline and glucose levels. Here we have used spontaneous hypertensive (SHR) and Wistar Kyoto (WKY) rats to investigate whether hypertension alters basal adrenal chromaffin cell function, or the response of these cells to acute 2DG treatment. At basal level, we found no differences in adrenal medulla TH protein, TH phosphorylation, TH activity or catecholamine levels between SHR and WKY despite a significant difference in the level of systolic blood pressure; nor were there differences in plasma catecholamine levels or blood glucose (BG). Furthermore, the vehicle animals evoked no significant changes in any parameter measured in SHR, but evoked significant increases in pSer19TH, plasma adrenaline and BG in WKY. Single episode of glucoprivation evoked increases in PKA and CDK/MAPK, pSer40TH, pSer31TH, TH activity, and plasma adrenaline and BG in SHR, and in addition evoked increases in PKC, CAMKII, and pSer19TH in WKY. These findings are significant which indicates hypertension does not impact catecholamine function in the adrenal gland. It also appears that hypertension does not alter the adrenal response to glucoprivation. The findings are also significant as WKY showed greater adrenal activation of protein kinases and TH phosphorylation in response to saline and 2DG when compared to SHR and possible reasons for these findings are further discussed.

Keywords: Adrenal gland; glucoprivation; hypertension; protein kinase; tyrosine hydroxylase

ABSTRAK

Kajian kami yang lepas telah menunjukkan bahawa pemberian intraperitoneal 2-deoksi-D-glukosa (2DG) akut kepada tikus Sprague-Dawley menyebabkan pengaktifan sel kromafin dalam medula adrenal yang ditunjukkan oleh peningkatan aktiviti protein kinase, pemfosforilan tirosina hidroksilase (TH), serta aras adrenalina dan plasma glukosa. Dalam kajian ini, kami telah menggunakan tikus hipertensi spontan (SHR) dan Wistar Kyoto (WKY) untuk mengkaji sama ada hipertensi akan mengubah fungsi bes sel kromafin adrenal serta tindak balas sel-sel tersebut terhadap rawatan 2DG akut. Pada peringkat bes, didapati tiada perbezaan pada aras protein TH, pemfosforilan TH, aktiviti TH atau aras katekolamina medula adrenal antara tikus SHR dan WKY walaupun terdapat perbezaan yang signifikan pada tahap tekanan darah sistolik; serta tiada perbezaan pada aras plasma katekolamina dan glukosa darah (BG). Tiada perubahan pada sebarang parameter yang diukur pada tikus pengangkut SHR, sebaliknya, terdapat peningkatan ketara pada pSer19TH, plasma adrenalina dan BG dalam tikus pengangkut WKY. Episod tunggal deprivasi glukosa mengakibatkan peningkatan pada PKA dan CDK/MAPK, pSer40TH, pSer31TH, aktiviti TH, plasma adrenalina dan BG dalam tikus SHR; di samping meningkatkan PKC, CAMKII dan pSer19TH pada tikus WKY. Hasil ini menunjukkan bahawa hipertensi tidak memberi kesan kepada fungsi katekolamina dalam kelenjar adrenal. Hipertensi turut tidak mengubah tindak balas adrenal kepada deprivasi glukosa. Tambahan pula, tikus WKY menunjukkan pengaktifan protein kinase dan pemfosforilan TH adrenal yang lebih tinggi sebagai tindak balas kepada saline dan 2DG berbanding SHR. Faktor yang mungkin menyebabkan penemuan ini turut dibincangkan dengan lebih lanjut.

Kata kunci: Deprivasi glukosa; hipertensi; kelenjar adrenal; protein kinase; tirosina hidroksilase

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*Corresponding author; email: hanafi.damanhuri@ppukm.ukm.edu.my