A prepro-TRH connecting peptide (prepro-TRH 160-169) potentiates TRH-induced TSH release from rat perifused pituitaries by stimulating dihydropyridine- and omega-conotoxin-sensitive Ca2+ channels.
The stimulation of TSH secretion by TRH involves the phosphatidylinositol second messenger pathway via activation of phospholipase C. This effect is mediated by a GTP-binding protein and leads to a mobilization of intracellular Ca2+ stores and an activation of protein kinase C. However, TRH stimulation also results in an influx of extracellular Ca2+. Since we have previously demonstrated that a non-TRH fragment of the prepro-TRH molecule, the connecting peptide PS4 (prepro-TRH 160-169), was able to potentiate the TRH-induced TSH release in a dose-dependent manner, we attempted to determine whether this potentiation might be due to a Ca(2+)-dependent phenomenon and whether a specific class of voltage-dependent Ca2+ channels, the L type Ca2+ channels, might be involved in the effect of PS4. This was studied by perifusing normal pituitary fragments with medium containing either the Ca2+ ionophore, ionomycin, and Co2+ ions, or organic compounds well known to block L-type Ca2+ channels, and by measuring the TSH response to a pulse of TRH (10 nM) in the presence or absence of PS4 (100 nM).(ABSTRACT TRUNCATED AT 250 WORDS)
Roussel
J P
JP
Laboratoire de Neurobiologie Endocrinologique, URA 1197 CNRS-Université de Montpellier 2, France.
Hollande
F
F
Bulant
M
M
Astier
H
H
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000502:physiology*; D004095:Dihydropyridines / Q000494:pharmacology; D008297:Male; D010446:Peptide Fragments / Q000494:pharmacology*; D010456:Peptides, Cyclic / Q000494:pharmacology; D010477:Perfusion / Q000379:methods; D010902:Pituitary Gland / Q000378:metabolism*; D011498:Protein Precursors / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013972:Thyrotropin / Q000378:metabolism*; D013973:Thyrotropin-Releasing Hormone / Q000494:pharmacology*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology; D020960:omega-Conotoxins
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D004095:Dihydropyridines; D010446:Peptide Fragments; D010456:Peptides, Cyclic; D011498:Protein Precursors; D010566:Virulence Factors, Bordetella; D020960:omega-Conotoxins; C053423:Conus magus toxin; C057639:prepro-thyrotropin releasing hormone (160-169); D013973:Thyrotropin-Releasing Hormone; C038806:1,4-dihydropyridine; D013972:Thyrotropin; D002118:Calcium