Stimulation of inositol phosphate formation in FRTL-5 rat thyroid cells by catecholamines and its relationship to changes in 45Ca2+ efflux and cyclic AMP accumulation.
Catecholamines specifically stimulated the rapid formation of inositol phosphates, bisphosphates and trisphosphates in a concentration-dependent manner in FRTL-5 thyroid cells. Further analysis by high performance liquid chromatography revealed the presence of two isomers of inositol trisphosphate, 1,4,5- and 1,3,4-trisphosphate, suggesting that the 1,4,5-trisphosphate of inositol is further metabolized to the 1,3,4-trisphosphate isomer. The alpha 1-adrenoreceptor antagonist, prazosin, inhibited the effects of epinephrine, while the alpha 2-adrenoreceptor antagonist, yohimbine, was without effect. Treatment of FRTL-5 cells with pertussis toxin (to inhibit Ni) did not abolish the epinephrine effect on inositol trisphosphate formation. Carbachol, N6-[L-2-phenylisopropyl]-adenosine and forskolin were without effect on phosphoinositide metabolism. Both epinephrine and the calcium ionophore A23187 stimulated 45Ca2+ efflux from 45Ca2+-loaded FRTL-5 cells. The time-course of the epinephrine effect indicates that inositol 1,4,5-trisphosphate formation (t1/2 approximately 1 s) precedes both the efflux of 45Ca2+ (t1/2 approximately 30 s) as well as the reduction of cyclic AMP levels (t1/2 approximately 90 s) in response to epinephrine. These results strongly suggest that inositol 1,4,5-trisphosphate has the appropriate properties to act as a second messenger by which alpha 1-adrenergic hormones, through mobilization of intracellular Ca2+ and activation of cyclic AMP phosphodiesterase, reduce cyclic AMP levels in FRTL-5 cells.
Berman
M I
MI
Department of Biochemistry and Nutrition, University of North Carolina, School of Medicine, Chapel Hill 27514.
Thomas
C G
CG
Nayfeh
S N
SN
D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002395:Catecholamines / Q000494:pharmacology*; D002478:Cells, Cultured; D002712:Chlorides / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D007295:Inositol Phosphates / Q000378:metabolism*; D008094:Lithium / Q000494:pharmacology; D018021:Lithium Chloride; D037342:Pertussis Toxin; D051381:Rats; D013403:Sugar Phosphates / Q000378:metabolism*; D013961:Thyroid Gland / Q000378:metabolism*; D013972:Thyrotropin / Q000494:pharmacology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D002395:Catecholamines; D002712:Chlorides; D007295:Inositol Phosphates; D013403:Sugar Phosphates; D010566:Virulence Factors, Bordetella; D000001:Calcimycin; D013972:Thyrotropin; D008094:Lithium; D000242:Cyclic AMP; D037342:Pertussis Toxin; D018021:Lithium Chloride; D002118:Calcium