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Goat brain enkephalin degrading enzyme: interaction with analgesic and antihypertensive drugs

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Abstract

Dipeptidylpeptidase (DPP) was purified from goat brain (Capra hircus) which acts on Arg-Arg-4mβNA and is functional homologue of mammalian DPP-III. The enzyme was found to hydrolyse enkephalin, angiotensin II and III, ACTH and gastrin tetrapeptide amide. As enkephalin is involved in pain modulation and angiotensins regulate the renin-angiotensin system, the effect of commonly used analgesic and antihypertensive drugs was screened on the activities of purified goat brain DPP. Among the analgesic drugs, diclofenac Na had the highest potency. In regards to mechanism of inhibition, diclofenac Na, paracetamol and rofecoxib inhibited the enzyme in competitive manner and nimesulide exhibited mixed inhibition for the enzyme with K i of 300, 245, 190, and 70 μM, respectively. All the studied antihypertensive drugs inhibited the enzyme in competitive manner with K i of 185, 230 and 280 μM for atenolol, metroprolol and labetalol, respectively.

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Acknowledgment

Suman Dhanda is thankful to University Grants Commission for providing the junior research fellowship.

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Correspondence to Suman Dhanda.

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Dhanda, S., Singh, J. & Singh, H. Goat brain enkephalin degrading enzyme: interaction with analgesic and antihypertensive drugs. Med Chem Res 20, 1294–1297 (2011). https://doi.org/10.1007/s00044-010-9454-7

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  • DOI: https://doi.org/10.1007/s00044-010-9454-7

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