Reduction of exogenous vasopressin RNA poly(A) tail length increases its effectiveness in transiently correcting diabetes insipidus in the Brattleboro rat.
Magnocellular hypothalamic neurons in Brattleboro rats can accumulate, transport, and translate exogenous [Arg8]vasopressin (AVP) mRNA after injection in the hypothalamo-hypophysial tract in amounts sufficient to reverse transiently the animals' characteristic diabetes insipidus. In the present study, different preparations of hypothalamic RNA extracted from normal rats or synthetic AVP RNA were injected into the lateral hypothalamus of Brattleboro rats. Poly(A)- RNA and poly(A)+ RNA from which tails were removed by RNase H digestion were much more effective than poly(A)+ RNA in expressing AVP in the magnocellular hypothalamic neurons and in raising urine osmolarity. Synthetic AVP RNA lacking a poly(A) tail also produced a very potent dose-dependent diabetes insipidus reversal. Our results suggest that a short or absent poly(A) tail may facilitate the accumulation, transport, or expression of exogenous AVP mRNA by magnocellular neurons.
Maciejewski-Lenoir
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Department of Neuropharmacology, Scripps Research Institute, La Jolla, CA 92037.
Jirikowski
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Sanna
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Bloom
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D000818:Animals; D001127:Arginine Vasopressin / Q000235:genetics*; D003919:Diabetes Insipidus / Q000235:genetics / Q000628:therapy*; D004305:Dose-Response Relationship, Drug; D007030:Hypothalamo-Hypophyseal System / Q000503:physiopathology*; D007031:Hypothalamus / Q000502:physiology; D011061:Poly A / Q000235:genetics / Q000302:isolation & purification / Q000627:therapeutic use*; D012313:RNA / Q000235:genetics / Q000302:isolation & purification / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D011910:Rats, Brattleboro; D011917:Rats, Inbred Lew
D012333:RNA, Messenger; D001127:Arginine Vasopressin; D011061:Poly A; D012313:RNA