title: Evolution of streptozotocin-pancreatic damage in the rat: modulatory effect of endothelins on the nitridergic and prostanoid pathway.
abstract: Many lines of evidence indicate that an increased pancreatic production of nitric oxide (NO) and prostaglandins (PGs) is found in the pancreas of streptozotocin-diabetic rats and that endothelins (ETs) are closely related to the nitridergic and prostanoid pathway in several tissues. In the present study the relationship between NO, ETs, and PGs has been explored in isolated pancreatic tissue from streptozotocin-diabetic rats. Pancreatic ET levels are higher in pancreatic tissues from diabetic (D) rats compared to control (C) animals. The addition of nitric oxide synthase (NOS) inhibitors (1 mM N(G)-nitro-l-arginine methyl ester, 600 microM N(G)-monomethyl-l-arginine) in the incubating medium reduces and NO donors (SIN-1, 300 microM spermine suppress, NONOate 100 microM) increases ET levels in pancreatic slices from C and D animals. PGE(2) (10(-7) M) increases and indomethacin (10(-6) M) decreases ET pancreatic production only in D but not in C tissues when added into the incubating bath. When tissues are incubated in the presence of endothelin 1 (ET-1) (10(-7) M), NOS activity is higher in C pancreas, while the ET-receptor antagonist bosentan (B) decreases NOS levels in D but not in C tissues. When pancreatic arachidonic acid (AA) conversion to prostaglandins was explored, ET-1 increased PGF(2alpha), PGE(2), and TXB(2) levels in C but not in D tissues. B abolishes TXB(2) increment due to the diabetic state, but failed in modulating AA conversion to 6-keto PGF(1alpha), PGF2(alpha) and PGE(2) in D pancreas. Our results show an alteration in AA metabolism, ET production, and NO increment associated with pancreatic damage due to streptozotocin.
authors.affiliation: Centro de Estudios Farmacológicos y Botánicos (CEFYBO), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Barcelona, Spain. elidate@arnet.com.ar
authors.forename: E
authors.initials: E
authors.lastname: González
authors.forename: A
authors.initials: A
authors.lastname: Jawerbaum
authors.forename: D
authors.initials: D
authors.lastname: Sinner
authors.forename: C
authors.initials: C
authors.lastname: Pustovrh
authors.forename: C
authors.initials: C
authors.lastname: Xaus
authors.forename: C
authors.initials: C
authors.lastname: Peralta
authors.forename: G
authors.initials: G
authors.lastname: Gómez
authors.forename: J
authors.initials: J
authors.lastname: Roselló-Catafau
authors.forename: E
authors.initials: E
authors.lastname: Gelpi
authors.forename: M
authors.initials: M
authors.lastname: Gimeno
mesh_terms: D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism* / Q000473:pathology; D015237:Dinoprost / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism / Q000494:pharmacology; D019332:Endothelin-1 / Q000494:pharmacology; D016232:Endothelins / Q000378:metabolism*; D008297:Male; D008981:Molsidomine / Q000031:analogs & derivatives / Q000494:pharmacology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D009589:Nitrogen Oxides; D010179:Pancreas / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D013096:Spermine / Q000031:analogs & derivatives / Q000494:pharmacology; D013311:Streptozocin / Q000633:toxicity*; D013929:Thromboxane B2 / Q000378:metabolism; D019323:omega-N-Methylarginine / Q000494:pharmacology
chemical_list: D019332:Endothelin-1; D016232:Endothelins; D020030:Nitric Oxide Donors; D009589:Nitrogen Oxides; C091861:spermine nitric oxide complex; D019323:omega-N-Methylarginine; D016718:Arachidonic Acid; D013096:Spermine; D009569:Nitric Oxide; D013929:Thromboxane B2; C002385:linsidomine; D013311:Streptozocin; D015237:Dinoprost; D008981:Molsidomine; D019001:Nitric Oxide Synthase; D015232:Dinoprostone; D019331:NG-Nitroarginine Methyl Ester