Add time:07/12/2019         Source:sciencedirect.com

We have recently shown that the tripeptide l-pyroglutamyl-lhistidyl-l-proline-amide (mammalian TRH) stimulates α-MSH secretion in amphibia. Using a perifusion system technique, we have compared the stereochemical requirements for hormone-receptor interaction of frog melanotrophs with mammalian thyrotrophs and mammatrophs. Of all the analogs tested, only the TRH analog l-N-(2-oxopiperidine-6-yl-carbonyl)-histidyl-thiazolidine-4-carboxamide (MK-771) was equipotent with TRH. All analogs which were known to be TRH agonists in mammals (e.g., [Pic]3-TRH, [Pro-hydrazide]3-TRH) were also relatively active on α-MSH release. Seven analogs were totally inactive on both mammalian pars distalis and frog pars intermedia. The discrepancies concerned only two TRH analogs in which the histidine moiety has been altered [Tyr]2-TRH and [Lys]2-TRH). The biological potencies of these analogs were 17 and 8% on α-MSH release whereas both molecules were devoid of activity in mammals.

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