Vasopressin antisense oligonucleotide induces temporary diabetes insipidus in rats.
The purpose of this study was to downregulate the transcriptional message of arginine vasopressin (AVP) by antisense treatment. A complete phosphorothioate antisense oligodesoxynucleotide corresponding to the beginning of the coding region of rat AVP mRNA was constructed and injected into the lateral ventricle of rats. Within 3-6 h animals exhibited a temporary diabetes insipidus, which lasted up to 9 h. Accordingly, vasopressin immunoreactivity in the hypothalamic nuclei was reduced. Our results demonstrate that a specific and reversible inhibition of neuropeptide expression can be accomplished in the intact hypothalamo-neurohypophysial system by antisense treatment, thus providing a novel tool for studies on stimulus-secretion coupling in vivo.
Skutella
T
T
Department of Neuroendocrinology, Max Planck Institute of Psychiatry, Munich, Germany.
Probst
J C
JC
Engelmann
M
M
Wotjak
C T
CT
Landgraf
R
R
Jirikowski
G F
GF
D000818:Animals; D001127:Arginine Vasopressin / Q000096:biosynthesis*; D001483:Base Sequence; D003919:Diabetes Insipidus / Q000139:chemically induced* / Q000652:urine; D015536:Down-Regulation / Q000187:drug effects; D007276:Injections, Intraventricular; D008297:Male; D008969:Molecular Sequence Data; D016376:Oligonucleotides, Antisense / Q000008:administration & dosage / Q000494:pharmacology*; D009994:Osmolar Concentration; D051381:Rats; D017208:Rats, Wistar
D016376:Oligonucleotides, Antisense; D001127:Arginine Vasopressin