Effects of Norepinephrine on Cyclic Nucleotide Levels in Dog Thyroid Slices*

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Abstract
In vitro effects of norepinephrine [NE] on cyclic nucleotide levels were studied in dog thyroid slices incubated in Krebs-Ringer bicarbonate buffer. NE (1-100 .mu.M) caused a rise in c[cyclic]AMP levels. By using the maximal dose of NE (100 .mu.M) the cAMP concentration reached a peak (about 200% of the basal) within 1 min and declined thereafter, returning to the basal level within 10 min. cGMP concentrations were increased by NE at concentrations higher than 10 .mu.M. The maximal dose of NE (100 .mu.M) caused a gradual increase in cGMP levels, reaching a peak of about 300% of the basal after 30 min. A .beta.-adrenergic blocking agent, propranolol (100 .mu.M), prevented the effect of NE on cAMP levels, but not on cGMP levels. Phentolamine, an .alpha.-adrenergic blocking agent, had little or no effect on NE stimulation of cAMP levels, although it caused a marked inhibition of the NE stimulation of cGMP levels. Slices incubated with NE exhibited a diminished responsiveness of the cAMP system when they were later reexposed to this catecholamine. Exclusion of Ca2+ from the buffer had no effect on the basal levels of cAMP and cGMP. Effects of NE on the cGMP levels were attenuated by removing Ca2+ from the buffer, whereas those effects on the cAMP were not influenced by this procedure. These findings indicate that in the dog thyroid gland, NE activates the cAMP system via .beta.-adrenergic receptors and the cGMP system via .alpha.-adrenergic receptors. Contrary to cGMP, stimulation of cAMP was not Ca2+-dependent.