Effects of thyroid-stimulating hormone, carbachol, norepinephrine, and adenosine 3',5'-monophosphate on polyphosphatidylinositol phosphate hydrolysis in dog thyroid slices.
TSH (10-250 mU/ml), carbachol (100 nM to 10 microM), and norepinephrine (10-100 microM) stimulated in a dose-dependent manner the accumulation of [3H]glycerophosphoinositol, [3H]inositol monophosphate, [3H]inositol bisphosphate, and [3H]inositol triphosphate in dog thyroid slices prelabeled with myo-[2-3H]inositol. The maximal effect of carbachol was considerably greater than that of TSH and norepinephrine. Carbachol stimulation of [3H]inositol phosphates (InsPs) was present by 5 min of incubation, while that of TSH required at least 30 min. Neither the basal level of [3H]InsPs nor the stimulation by carbachol (1 microM) or norepinephrine (500 microM) was affected by forskolin (10 microM) or cAMP analogs [8-bromo-cAMP or (Bu)2-cAMP; 1 mM]. A maximal amount of TSH (250 mU/ml) had ergistic effects on submaximal carbachol (1 microM)- and additive effects on maximal norepinephrine (500 microM)-induced accumulation of [3H]InsPs. Since not all of the effects of TSH on the thyroid can be explained by activation of the adenylate cyclase system, these data indicate that TSH may also regulate thyroid function through the polyphosphatidylinositol phosphate pathway. In addition, stimulation of the adenylate cyclase-cAMP system does not modify the effects of carbachol or norepinephrine on [3H]InsPs accumulation in dog thyroid slices.
Taguchi
M
M
St. Luke's Episcopal Hospital, Department of Medicine, Baylor College of Medicine, Houston, Texas 77030.
Field
J B
JB
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology*; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000502:physiology*; D004285:Dogs; D006868:Hydrolysis; D066298:In Vitro Techniques; D007295:Inositol Phosphates / Q000378:metabolism; D007700:Kinetics; D009638:Norepinephrine / Q000494:pharmacology*; D018129:Phosphatidylinositol Phosphates; D010716:Phosphatidylinositols / Q000378:metabolism*; D012016:Reference Values; D013961:Thyroid Gland / Q000187:drug effects / Q000378:metabolism*; D013972:Thyrotropin / Q000494:pharmacology*
D007295:Inositol Phosphates; D018129:Phosphatidylinositol Phosphates; D010716:Phosphatidylinositols; D005576:Colforsin; D015124:8-Bromo Cyclic Adenosine Monophosphate; D003994:Bucladesine; D002217:Carbachol; D013972:Thyrotropin; D000242:Cyclic AMP; D009638:Norepinephrine