Aspartyl, arginyl and alanyl aminopeptidase activities in the hippocampus and hypothalamus of streptozotocin-induced diabetic rats.
Acid (aspartyl), basic (arginyl) and neutral (alanyl) aminopeptidases degrade angiotensins, vasopressin, oxytocin, bradykinin and enkephalins. These peptides regulate memory, energy homeostasis, water-salt balance and blood pressure, functions that are mainly exerted in the hippocampus and hypothalamus, and that can be affected by diabetes mellitus. To evaluate the relationship between the diabetes mellitus and processing and inactivation roles of these representative aminopeptidases, we measured their activities in both brain structures of control and streptozotocin-diabetic rats. Hypothalamic soluble aspartyl and arginyl aminopeptidases presented significant decreased activity levels in diabetic rats, which were mitigated by insulin therapy. In addition to membrane-bound puromycin sensitive and insensitive alanyl aminopeptidases, its soluble puromycin sensitive form did not differ between diabetic and control rats in both brain structures. Glucose and/or insulin did not seem to alter in vitro the hypothalamic activities of soluble aspartyl and arginyl aminopeptidases. The implied hypothalamic control of regulatory peptide activity by aspartyl and arginyl aminopeptidases supports the hypothesis that the hydrolytic ability of these enzyme types could be a common link for the disruptions of water-salt balance, blood pressure and energy homeostasis in diabetes mellitus.
Zambotti-Villela
Leonardo
L
Laboratory of Pharmacology, Instituto Butantan, Av. Vital Brazil, 1500, 05503-900 São Paulo, SP, Brazil.
Yamasaki
Simone C
SC
Villarroel
Joyce S
JS
Alponti
Rafaela F
RF
Silveira
Paulo F
PF
D000626:Aminopeptidases / Q000032:analysis / Q000378:metabolism*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D001928:Brain Diseases, Metabolic / Q000201:enzymology* / Q000209:etiology* / Q000503:physiopathology; D018826:CD13 Antigens / Q000032:analysis / Q000378:metabolism; D002462:Cell Membrane / Q000187:drug effects / Q000201:enzymology; D003921:Diabetes Mellitus, Experimental / Q000150:complications*; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D004700:Endocrine System Diseases / Q000201:enzymology / Q000209:etiology / Q000503:physiopathology; D043384:Glutamyl Aminopeptidase / Q000032:analysis / Q000378:metabolism; D006624:Hippocampus / Q000201:enzymology* / Q000503:physiopathology; D006706:Homeostasis / Q000502:physiology; D007031:Hypothalamus / Q000201:enzymology* / Q000503:physiopathology; D007328:Insulin / Q000378:metabolism / Q000494:pharmacology; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000201:enzymology; D009479:Neuropeptides / Q000378:metabolism; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D011691:Puromycin / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D014882:Water-Electrolyte Balance / Q000502:physiology
D007328:Insulin; D009479:Neuropeptides; D011500:Protein Synthesis Inhibitors; D011691:Puromycin; D000626:Aminopeptidases; D018826:CD13 Antigens; C019721:aminopeptidase B; D043384:Glutamyl Aminopeptidase