title: Synthesis and neuromodulatory effects of TRH-related peptides: inhibitory activity on catecholamine release in vitro.
abstract: BACKGROUND
  A detailed comprehension of central mechanisms underlying feeding behavior holds considerable promise for the treatment of alimentary disorders.
  
  
  METHODS
  In order to elucidate the tight interrelationships occurring at the hypothalamic neuronal endings between aminergic neurotransmitters and co-localized appetite modulators, we initially studied the effects of two anorexigenic peptides structurally related to thyrotropin-releasing hormone (TRH, 1), namely cyclo(His-Pro) (CHP, 2) and pGlu-His-Gly-OH (3), on [(3)H]-norepinephrine and [(3)H]-dopamine release from perfused rat hypothalamic synaptosomes. Furthermore, a number of TRH and CHP analogues were synthesized and tested for their ability to influence neurotransmitter release in the selected neuronal model.
  
  
  RESULTS
  Peptide 3 showed only a slight inhibitory activity on norepinephrine release, whereas no effect was observed for compound 2. TRH analogue 8, metabolically stabilized by the replacement of pyroglutamate with the pyrohomocysteic acid (pHcs), was found to be inactive. Conversely, a significant inhibitory effect on dopamine and norepinephrine release was observed for the CHP-related diketopiperazines cyclo(Leu-Pro) (11) and cyclo(His-Gly) (14).
  
  
  CONCLUSIONS
  These results suggest a potential role for cyclo-dipeptides 11 and 14 in the hypothalamic modulation of appetite suppressant circuitry.
authors.affiliation: Department of Pharmacy, G. d'Annunzio University, via dei Vestini 31, 66013 Chieti, Italy. mvacca@unich.it.
authors.forename: Luigi
authors.initials: L
authors.lastname: Brunetti
authors.forename: Annalisa
authors.initials: A
authors.lastname: Chiavaroli
authors.forename: Alessandra
authors.initials: A
authors.lastname: Cocco
authors.forename: Claudio
authors.initials: C
authors.lastname: Ferrante
authors.forename: Anna
authors.initials: A
authors.lastname: Ferrucci
authors.forename: Grazia
authors.initials: G
authors.lastname: Luisi
authors.forename: Giustino
authors.initials: G
authors.lastname: Orlando
authors.forename: Francesco
authors.initials: F
authors.lastname: Pinnen
authors.forename: Michele
authors.initials: M
authors.lastname: Vacca
mesh_terms: D000818:Animals; D002395:Catecholamines / Q000378:metabolism*; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009842:Oligopeptides / Q000138:chemical synthesis / Q000494:pharmacology*; D010455:Peptides / Q000138:chemical synthesis* / Q000494:pharmacology*; D010456:Peptides, Cyclic / Q000138:chemical synthesis / Q000494:pharmacology*; D010879:Piperazines / Q000138:chemical synthesis / Q000494:pharmacology*; D011761:Pyrrolidonecarboxylic Acid / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D051381:Rats; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism; D013973:Thyrotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000494:pharmacology*
chemical_list: D002395:Catecholamines; D009842:Oligopeptides; D010455:Peptides; D010456:Peptides, Cyclic; D010879:Piperazines; D013973:Thyrotropin-Releasing Hormone; C023866:pyroglutamyl-histidyl-glycine; C015924:histidyl-proline diketopiperazine; D011761:Pyrrolidonecarboxylic Acid