Hyperthyroid adult rat cardiomyocytes. I. Nucleotide content, beta- and alpha-adrenoreceptors, and cAMP production

Am J Physiol. 1989 Nov;257(5 Pt 1):C948-56. doi: 10.1152/ajpcell.1989.257.5.C948.

Abstract

Ventricular myocytes isolated from the hypertrophied hearts of thyrotoxic adult rats have an increase in mean protein content per myocyte (6.3 +/- 0.2 vs. 4.4 +/- 0.2 ng) compared with euthyroid cells. Viability and adenine nucleotide profiles are similar in both populations, but NAD content of the hyperthyroid myocytes is depressed (4.9 +/- 0.2 vs. 5.5 +/- 0.2 nmol/mg for controls) and UTP is higher (1.2 +/- 0.09 vs. 0.9 +/- 0.04 nmol/mg). Binding of (-)-[125I]iodocyanopindolol to intact hyperthyroid myocytes is increased by 42% compared with controls, with no change in the dissociation constant (Kd). This elevation in beta-receptor number is correlated to enhanced beta-agonist-induced adenosine 3',5'-cyclic monophosphate (cAMP) production. The half-maximal effective concentration (EC50) for the euthyroid isoproterenol dose-response curve is 2.14 x 10(-7) M but is decreased to 2.51 x 10(-8) M in hyperthyroid cardiac cells. Basal adenylate cyclase activity is apparently not affected by thyroid hormones, since basal cAMP levels for both groups are identical (5 pmol/mg) and both rise roughly twofold in the presence of a phosphodiesterase inhibitor. Forskolin-induced cAMP production and cAMP-specific phosphodiesterase activity are similar as well. In contrast to beta-adrenergic response, there are no significant differences in alpha 1-antagonist [3H]prazosin binding parameters between hyperthyroid and euthyroid cardiomyocytes.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 1-Methyl-3-isobutylxanthine / pharmacology
  • 3',5'-Cyclic-AMP Phosphodiesterases / metabolism
  • AMP Deaminase / metabolism
  • Animals
  • Binding Sites
  • Colforsin / pharmacology
  • Cyclic AMP / biosynthesis*
  • Enzyme Activation
  • Hyperthyroidism / metabolism*
  • Hyperthyroidism / pathology
  • Myocardium / metabolism*
  • Myocardium / pathology
  • Nucleotides / metabolism
  • Phenylephrine / pharmacology
  • Rats
  • Receptors, Adrenergic, alpha / metabolism*
  • Receptors, Adrenergic, beta / metabolism*

Substances

  • Nucleotides
  • Receptors, Adrenergic, alpha
  • Receptors, Adrenergic, beta
  • Colforsin
  • Phenylephrine
  • Cyclic AMP
  • 3',5'-Cyclic-AMP Phosphodiesterases
  • AMP Deaminase
  • 1-Methyl-3-isobutylxanthine