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)