In-vitro and in-vivo antagonistic action of an anti-amylin Spiegelmer.
The anorectic and dipsogenic effects of the pancreatic hormone amylin are mediated by the area postrema and the subfornical organ. We tested the effectiveness of a new amylin antagonist, a so-called RNA Spiegelmer, by electrophysiological in-vitro recordings from the rat subfornical organ and by immunohistological c-Fos studies in the area postrema. Amylin's excitatory effect on subfornical organ neurons was blocked by the anti-amylin Spiegelmer. Peripheral administration 5 h prior to amylin also suppressed the amylin-induced activation (c-Fos expression) in the area postrema. The biostable anti-amylin Spiegelmer may be therapeutically beneficial in conditions associated with high plasma amylin levels, such as cancer anorexia occurring during certain pancreatic tumors.
Bilik
Kerstin U
KU
Institute of Veterinary Physiology, University of Zurich, Zurich, Switzerland.
Ergüven
Elif
E
Klussmann
Sven
S
Jarosch
Florian
F
Wielinga
Peter Y
PY
Lutz
Thomas A
TA
Riediger
Thomas
T
D000682:Amyloid / Q000037:antagonists & inhibitors* / Q000235:genetics; D000818:Animals; D052157:Aptamers, Nucleotide / Q000494:pharmacology*; D031608:Area Postrema / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D004594:Electrophysiology; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D058228:Islet Amyloid Polypeptide; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009474:Neurons / Q000187:drug effects; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D013356:Subfornical Organ / Q000166:cytology / Q000187:drug effects / Q000502:physiology*
D000682:Amyloid; D052157:Aptamers, Nucleotide; D058228:Islet Amyloid Polypeptide; C525629:NOX-A42; D016760:Proto-Oncogene Proteins c-fos