On the involvement of cyclic AMP and extracellular Ca2+ in the regulation of hormone release from rat pituitary tumour (GH3) cells in culture.
Thyroliberin (TRH), dibutyryl cyclic AMP (db-cAMP), and 3-isobutyl-1-methylxanthine (MIX) had a stimulatory effect on prolactin (PRL) and growth hormone (GH) release from GH3 cells. Half-maximal and maximal effects were observed for TRH at 2.5 nM and 10 nM; for db-cAMP at 0.6 mM and 5 mM, respectively. MIX (0.1 mM-1 mM) induced a dose-dependent accumulation of cellular cyclic AMP, while the hormone release was already maximally stimulated at 0.1 mM MIX. The maximal effects on hormone release of TRH and db-cAMP, but not of TRH and MIX, were additive. The Ca2+ channel blockers Co2+ (5 mM) and verapamil (100 microM) and the Ca2+ chelator EGTA (4 mM) abolished the stimulatory effect of TRH (1 microM) on hormone release. Co2+ and verapamil, but not EGTA, inhibited the stimulatory effect of db-cAMP (5 mM) on hormone release. The inhibitory effects of Co2+ and verapamil on GH release were counteracted by the combination of TRH and db-cAMP. For PRL release Co2+, but not verapamil, was able to inhibit the combined action of TRH and db-cAMP. Co2+, verapamil, and EGTA eliminated the stimulatory effect of MIX (1 mM) on PRL release while only Co2+ and EGTA affected the GH release. Hormone release in the presence of MIX plus verapamil or EGTA, but not Co2+, was increased by TRH. The calmodulin antagonist trifluoperazine (TFP) at 30 microM inhibited basal hormone release and hormone release stimulated by TRH (1 microM), db-cAMP (5 mM), and MIX (1 mM). The Ca2+ ionophore A23187 (5 microM) had a stimulatory effect on basal hormone release which was abolished by 30 microM TFP.
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000502:physiology*; D002460:Cell Line; D003035:Cobalt / Q000494:pharmacology; D000242:Cyclic AMP / Q000502:physiology*; D004533:Egtazic Acid / Q000494:pharmacology; D005110:Extracellular Space / Q000502:physiology; D013006:Growth Hormone / Q000378:metabolism*; D010911:Pituitary Neoplasms / Q000378:metabolism*; D011388:Prolactin / Q000378:metabolism*; D051381:Rats; D013973:Thyrotropin-Releasing Hormone / Q000494:pharmacology; D014268:Trifluoperazine / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology
D014268:Trifluoperazine; D000001:Calcimycin; D003035:Cobalt; D004533:Egtazic Acid; D013973:Thyrotropin-Releasing Hormone; D003994:Bucladesine; D011388:Prolactin; D013006:Growth Hormone; D014700:Verapamil; D000242:Cyclic AMP; D002118:Calcium; D015056:1-Methyl-3-isobutylxanthine