Document Detail


A new oxytocin-saporin cytotoxin for lesioning oxytocin-receptive neurons in the rat hindbrain.
MedLine Citation:
PMID:  20610562     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Evidence suggests that release of oxytocin in the nucleus tractus solitarius (NTS) of the hindbrain from descending projections that originate in the paraventricular nucleus can inhibit food intake by amplifying the satiety response to cholecystokinin (CCK). To further evaluate this mechanism in rats, we used a novel cytotoxin, saporin conjugated to oxytocin (OXY-SAP), a compound designed to destroy cells that express oxytocin receptors (OXYr). OXY-SAP was injected directly into the NTS to lesion neurons that express OXYr and that are implicated in potentiating CCK's satiety effects. The control consisted of injection of saporin conjugated to a nonsense peptide. We found that OXY-SAP was cytotoxic to human uterine smooth muscle cells in vitro, demonstrating that OXY-SAP can lesion cells that express OXYr. Using laser capture microdissection and real-time quantitative PCR, we demonstrated that OXYr mRNA levels were reduced in the NTS after OXY-SAP administration. Moreover, we found that OXY-SAP attenuated the efficacy of CCK-8 to reduce food intake and blocked the actions of an OXYr antagonist to stimulate food intake. The findings suggest that OXY-SAP is an effective neurotoxin for in vivo elimination of cells that express OXYr and is potentially useful for studies to analyze central nervous system mechanisms that involve the action of oxytocin on food intake and other physiological processes.
Authors:
Denis G Baskin; Francis Kim; Richard W Gelling; Brian J Russell; Michael W Schwartz; Gregory J Morton; Hyagriv N Simhan; Daniel H Moralejo; James E Blevins
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2010-07-07
Journal Detail:
Title:  Endocrinology     Volume:  151     ISSN:  1945-7170     ISO Abbreviation:  Endocrinology     Publication Date:  2010 Sep 
Date Detail:
Created Date:  2010-08-25     Completed Date:  2010-10-04     Revised Date:  2011-09-13    
Medline Journal Info:
Nlm Unique ID:  0375040     Medline TA:  Endocrinology     Country:  United States    
Other Details:
Languages:  eng     Pagination:  4207-13     Citation Subset:  AIM; IM    
Affiliation:
Office of Research and Development Medical Research Service, Veterans Affairs Puget Sound Health Care System, Department of Veterans Affairs Medical Center, Seattle, Washington 98108, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cell Survival / drug effects
Cells, Cultured
Cytotoxins / chemistry,  pharmacology
Dose-Response Relationship, Drug
Eating / drug effects
Female
Gene Expression / drug effects
Humans
Interleukin-1beta / genetics
Male
Myometrium / cytology
Neurons / drug effects*,  metabolism,  pathology
Oxytocin / chemistry,  pharmacology*
Rats
Rats, Wistar
Receptors, Oxytocin / antagonists & inhibitors,  genetics*
Reverse Transcriptase Polymerase Chain Reaction
Rhombencephalon / drug effects,  metabolism,  pathology
Ribosome Inactivating Proteins, Type 1 / chemistry,  pharmacology*
Sincalide / pharmacology
Tumor Necrosis Factor-alpha / genetics
Grant Support
ID/Acronym/Agency:
DK17047/DK/NIDDK NIH HHS; P01 DK068384/DK/NIDDK NIH HHS; P30 DK017047/DK/NIDDK NIH HHS; P30 DK035816/DK/NIDDK NIH HHS; R01 DK052989-14/DK/NIDDK NIH HHS; R01 DK083042-17/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Cytotoxins; 0/Interleukin-1beta; 0/Receptors, Oxytocin; 0/Ribosome Inactivating Proteins, Type 1; 0/Tumor Necrosis Factor-alpha; 25126-32-3/Sincalide; 50-56-6/Oxytocin; EC 3.2.2.22/saporin
Comments/Corrections

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