Alpha 1-adrenergic regulation of TSH-stimulated cyclic AMP accumulation in rat thyroid cells.
Addition of epinephrine to cultured FRTL-5 rat thyroid cells led to a concentration-dependent reduction of TSH- and forskolin-stimulated cAMP accumulation. Clonidine, which preferentially activates the alpha 2-adrenoreceptor, had no effect on cAMP levels. The reduction of cAMP levels by epinephrine was selectively blocked by prazosin, an alpha 1-adrenoreceptor antagonist, but not by yohimbine, an alpha 2-adrenoreceptor antagonist. Pretreatment of FRTL-5 cells with pertussis toxin failed to abolish the inhibitory effect of epinephrine on cAMP accumulation. The bioactivity of the pertussis toxin preparation in this cell line was verified by its ability to ADP-ribosylate the alpha-subunit of the inhibitory guanine nucleotide regulatory protein, Ni, as well as its ability to abolish the inhibitory effect of N6-[L-2-phenylisopropyl]-adenosine on TSH-stimulated cAMP formation. The inhibitory effect of epinephrine on cAMP levels was dependent on Ca2+ and was reversed by 3-isobutyl-1-methylxanthine. Taken together, these results suggest that epinephrine reduces cAMP levels via alpha 1-adrenoreceptors. The failure of pertussis toxin to abolish this alpha-adrenergic effect is consistent with the conclusion that epinephrine-induced attenuation of cAMP accumulation occurs through activation of a Ca2+-calmodulin-sensitive phosphodiesterase and does not involve Ni or Ni-like proteins.
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000246:Adenosine Diphosphate Ribose / Q000378:metabolism; D000818:Animals; D002395:Catecholamines / Q000494:pharmacology; D002460:Cell Line; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000502:physiology*; D019204:GTP-Binding Proteins / Q000502:physiology; D037342:Pertussis Toxin; D010660:Phenylisopropyladenosine / Q000494:pharmacology; D051381:Rats; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*; D013961:Thyroid Gland / Q000502:physiology*; D013972:Thyrotropin / Q000494:pharmacology*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D002395:Catecholamines; D011942:Receptors, Adrenergic, alpha; D010566:Virulence Factors, Bordetella; D005576:Colforsin; D000246:Adenosine Diphosphate Ribose; D010660:Phenylisopropyladenosine; D013972:Thyrotropin; D000242:Cyclic AMP; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; D015056:1-Methyl-3-isobutylxanthine