Matches in SemOpenAlex for { <https://semopenalex.org/work/W2009045296> ?p ?o ?g. }
Showing items 1 to 91 of
91
with 100 items per page.
- W2009045296 endingPage "1190" @default.
- W2009045296 startingPage "1184" @default.
- W2009045296 abstract "Experimentally and clinically, treatment with high-doses of TRH produces a net excitation of spinal lower motor neurons (LMNs) that is subsequently reduced or completely lost through continuous or repeated exposure to the peptide. This is operationally termed “autorefractoriness” (AR). We have performed biochemical and in vivo pharmacologic experiments to investigate the mechanism(s) of AR. Biochemically, we classified TRH and several analogs into three groups based on their binding by spinalcord TRH-receptors (TRH-Rs): high-affinity, (low nanomolar range; MeTRH, TRH); intermediate-affinity (mid-nanomolar range; MK-771, RX77368) or low-affinity (micromolar range; DN-1417, PNP). When tested in vivo for LMN excitatory activity in cordotomized (T8) rats, TRH and MK-771 produced rapid-onset excitation followed by AR. In contrast, sustained excitation with much less AR was produced by the low affinity analog DN-1417. Based on these results, we have formulated two receptor-based hypotheses to explain AR: a) rapid TRH-R desensitization (conversion to an inactive form) by high- but not low-affinity TRH-analogs; and b) a slower down-regulation (cellular internalization) of the agonist-receptor complex, most evident with high-affinity agonists. Thus, low- rather than high-affinity TRH-analogs may be superior to TRH for providing sustained LMN excitation (increase of strength) in motor neuron degenerative disorders." @default.
- W2009045296 created "2016-06-24" @default.
- W2009045296 creator A5057574174 @default.
- W2009045296 creator A5066764553 @default.
- W2009045296 creator A5070314577 @default.
- W2009045296 creator A5043415475 @default.
- W2009045296 date "1986-08-01" @default.
- W2009045296 modified "2023-10-14" @default.
- W2009045296 title "Analogs of thyrotropin-releasing hormone: Hypotheses relating receptor binding to net excitation of spinal lower motor neurons" @default.
- W2009045296 cites W1490977436 @default.
- W2009045296 cites W1491546167 @default.
- W2009045296 cites W1574916849 @default.
- W2009045296 cites W1964994881 @default.
- W2009045296 cites W1976890368 @default.
- W2009045296 cites W1980362986 @default.
- W2009045296 cites W1994924540 @default.
- W2009045296 cites W2003217588 @default.
- W2009045296 cites W2008671882 @default.
- W2009045296 cites W2010216377 @default.
- W2009045296 cites W2016037437 @default.
- W2009045296 cites W2030805055 @default.
- W2009045296 cites W2035514830 @default.
- W2009045296 cites W2072125978 @default.
- W2009045296 cites W2074631079 @default.
- W2009045296 cites W2085381295 @default.
- W2009045296 cites W2089124835 @default.
- W2009045296 doi "https://doi.org/10.1016/s0006-291x(86)80407-7" @default.
- W2009045296 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/3019335" @default.
- W2009045296 hasPublicationYear "1986" @default.
- W2009045296 type Work @default.
- W2009045296 sameAs 2009045296 @default.
- W2009045296 citedByCount "20" @default.
- W2009045296 crossrefType "journal-article" @default.
- W2009045296 hasAuthorship W2009045296A5043415475 @default.
- W2009045296 hasAuthorship W2009045296A5057574174 @default.
- W2009045296 hasAuthorship W2009045296A5066764553 @default.
- W2009045296 hasAuthorship W2009045296A5070314577 @default.
- W2009045296 hasConcept C112592302 @default.
- W2009045296 hasConcept C12554922 @default.
- W2009045296 hasConcept C126322002 @default.
- W2009045296 hasConcept C134018914 @default.
- W2009045296 hasConcept C139770010 @default.
- W2009045296 hasConcept C150903083 @default.
- W2009045296 hasConcept C170493617 @default.
- W2009045296 hasConcept C185592680 @default.
- W2009045296 hasConcept C207001950 @default.
- W2009045296 hasConcept C2776216936 @default.
- W2009045296 hasConcept C2778938600 @default.
- W2009045296 hasConcept C2779779143 @default.
- W2009045296 hasConcept C55493867 @default.
- W2009045296 hasConcept C71315377 @default.
- W2009045296 hasConcept C71924100 @default.
- W2009045296 hasConcept C86803240 @default.
- W2009045296 hasConceptScore W2009045296C112592302 @default.
- W2009045296 hasConceptScore W2009045296C12554922 @default.
- W2009045296 hasConceptScore W2009045296C126322002 @default.
- W2009045296 hasConceptScore W2009045296C134018914 @default.
- W2009045296 hasConceptScore W2009045296C139770010 @default.
- W2009045296 hasConceptScore W2009045296C150903083 @default.
- W2009045296 hasConceptScore W2009045296C170493617 @default.
- W2009045296 hasConceptScore W2009045296C185592680 @default.
- W2009045296 hasConceptScore W2009045296C207001950 @default.
- W2009045296 hasConceptScore W2009045296C2776216936 @default.
- W2009045296 hasConceptScore W2009045296C2778938600 @default.
- W2009045296 hasConceptScore W2009045296C2779779143 @default.
- W2009045296 hasConceptScore W2009045296C55493867 @default.
- W2009045296 hasConceptScore W2009045296C71315377 @default.
- W2009045296 hasConceptScore W2009045296C71924100 @default.
- W2009045296 hasConceptScore W2009045296C86803240 @default.
- W2009045296 hasIssue "3" @default.
- W2009045296 hasLocation W20090452961 @default.
- W2009045296 hasLocation W20090452962 @default.
- W2009045296 hasOpenAccess W2009045296 @default.
- W2009045296 hasPrimaryLocation W20090452961 @default.
- W2009045296 hasRelatedWork W1995816823 @default.
- W2009045296 hasRelatedWork W2026857001 @default.
- W2009045296 hasRelatedWork W2027938488 @default.
- W2009045296 hasRelatedWork W2033209790 @default.
- W2009045296 hasRelatedWork W2033894260 @default.
- W2009045296 hasRelatedWork W2080367469 @default.
- W2009045296 hasRelatedWork W2106532285 @default.
- W2009045296 hasRelatedWork W2146333229 @default.
- W2009045296 hasRelatedWork W4290399282 @default.
- W2009045296 hasRelatedWork W4571987 @default.
- W2009045296 hasVolume "138" @default.
- W2009045296 isParatext "false" @default.
- W2009045296 isRetracted "false" @default.
- W2009045296 magId "2009045296" @default.
- W2009045296 workType "article" @default.