Effects of adenosine and adenosine A2A receptor agonist on motor nerve conduction velocity and nerve blood flow in experimental diabetic neuropathy.
This study examined the effects of chronic administration of adenosine and CGS 21680 hydrochloride (adenosine A(2A) receptor agonist) on motor nerve conduction velocity (MNCV), nerve blood flow (NBF) and histology of sciatic nerve in animal model of diabetic neuropathy. Adenosinergic agents were administered for 2 weeks after 6 weeks of streptozotocin-induced (50 mg/kg i.p.) diabetes in male Sprague-Dawley rats. Significant reduction in sciatic MNCV and NBF were observed after 8 weeks in diabetic animals in comparison with control (non diabetic) rats. Adenosine (10 mg/kg, i.p.) significantly improved sciatic MNCV and NBF in diabetic rats. The protective effect of adenosine on MNCV and NBF was completely reversed by theophylline (50 mg/kg, i.p.), a non-selective adenosine receptor antagonist, suggesting that the adenosine effect was mediated via adenosinergic receptors. CGS 21680 (0.1 mg/kg, i.p.) significantly improved NBF; however, MNCV was not significantly improved in diabetic rats. At a dose of 1 mg/kg, neither MNCV nor NBF was improved by CGS 21680 in diabetic rats. ZM 241385 (adenosine A(2A) receptor antagonist) prevented the effect of CGS 21680 (0.1 mg/kg, i.p.). Histological changes observed in sciatic nerve were partially improved by the adenosinergic agents in diabetic rats. Results of the present study, suggest the potential of adenosinergic agents in the therapy of diabetic neuropathy.
Kumar
Sokindra
S
Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Sec-67, SAS Nagar, Punjab-160062, India.
Arun
K H S
KH
Kaul
Chaman L
CL
Sharma
Shyam S
SS
D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D009431:Neural Conduction / Q000187:drug effects*; D010627:Phenethylamines / Q000494:pharmacology; D058910:Purinergic P2 Receptor Agonists; D051381:Rats; D012039:Regional Blood Flow / Q000187:drug effects; D012584:Sciatic Nerve / Q000098:blood supply / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D013194:Staining and Labeling / Q000379:methods; D013311:Streptozocin; D013806:Theophylline / Q000494:pharmacology; D013997:Time Factors; D014227:Triazines / Q000494:pharmacology; D014230:Triazoles / Q000494:pharmacology
D001786:Blood Glucose; D010627:Phenethylamines; D058910:Purinergic P2 Receptor Agonists; D014227:Triazines; D014230:Triazoles; C097270:ZM 241385; C061282:2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine; D013311:Streptozocin; D013806:Theophylline; D000241:Adenosine