Blockade of potassium or calcium channels provokes modifications in TRH-induced TSH release from rat perifused pituitaries.
The aim of the present study was to determine the functional relationship between blockade of potassium or calcium channel activity and the initial burst of TSH secretion in response to TRH. Perifused rat pituitary fragments were stimulated by a 6-min pulse of physiological concentration of TRH (10 nM) in the presence or absence of pharmacological blockers of K+ or Ca2+ channels. Blockade of Ca(2+)-activated K+ channels with TEA (10 mM and 30 mM), apamin (200 nM), or charybdotoxin (50 nM) completely or partially blunted TRH-induced TSH release. By contrast, blockade of voltage-dependent K+ channels with 4-aminopyridine (4-AP) (500 microM) or with dendrotoxin (DTX) (350 nM) significantly increased TSH response. Moreover, blockade of T-type voltage-sensitive Ca2+ channels (VSCC) with NiCl (3 mM) or with diphenylhydantoin (100 microM) significantly (P < 0.01) reduced TSH response to TRH, whereas blockade of L-type Ca2+ channels with verapamil (50 microM) was ineffective. Our results suggest that secretion of TSH in response to nanomolar concentrations of TRH is correlated with stimulation of Ca(2+)-activated K+ channels, and inhibition of 4-AP-and DTX-sensitive voltage-dependent K+ channels; furthermore TSH response seems to depend on the activation of T-type VSCC.
Roussel
J P
JP
Laboratoire de Neurobiologie Endocrinologique, URA 1197 CNRS, Université de Montpellier 2, France.
Mateu
G
G
Astier
H
H
D000818:Animals; D001030:Apamin / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D018999:Charybdotoxin; D004546:Elapid Venoms / Q000494:pharmacology; D008297:Male; D009532:Nickel / Q000494:pharmacology; D010672:Phenytoin / Q000494:pharmacology; D010902:Pituitary Gland / Q000187:drug effects / Q000378:metabolism*; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D012604:Scorpion Venoms / Q000494:pharmacology; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000494:pharmacology; D013972:Thyrotropin / Q000378:metabolism*; D013973:Thyrotropin-Releasing Hormone / Q000494:pharmacology*
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D004546:Elapid Venoms; D015221:Potassium Channels; D012604:Scorpion Venoms; D013757:Tetraethylammonium Compounds; D018999:Charybdotoxin; D001030:Apamin; D013973:Thyrotropin-Releasing Hormone; D010672:Phenytoin; D019789:Tetraethylammonium; C022838:nickel chloride; C020273:dendrotoxin; D009532:Nickel; D013972:Thyrotropin; D002118:Calcium