Effect of thyroid status on beta-adrenoceptors and calcium channels in rat cardiac and vascular tissue.
To determine the influence of thyroid hormone on beta-adrenoceptors and Ca2+ channels, rats were treated with thyroxine (75 micrograms/100 g sc daily for 5 days) or propylthiouracil (0.05% in drinking water for 30 days). beta-Adrenoceptor density in ventricular tissue, measured by [125I]iodocyanopindolol binding, was significantly increased and decreased respectively, following thyroxine or propylthiouracil treatment to 124.7 +/- 7.11 fmol/mg protein and 71.98 +/- 5.37 fmol/mg protein from euthyroid (control) levels of 93.7 +/- 4.58 fmol/mg protein. Ca2+ channel density, measured by [3H]nitrendipine binding, was altered in the opposite direction; it was significantly decreased and increased to 324 +/- 24 fmol/mg protein and 691 +/- 31 fmol/mg protein from 562 +/- 35 fmol/mg protein after thyroxine or propylthiouracil treatment, respectively. No changes in affinity of either ligand were observed. Responses of isolated papillary muscles from propylthiouracil-treated animals accorded with changes seen in the binding studies. The geometric mean EC50 of isoproterenol increased from 9.5 x 10(-9) mol/l to 5.5 x 10(-8) mol/l, and the EC50 for calcium decreased from 3.16 x 10(-3) mol/l to 1.36 x 10(-3) mol/l; moreover, the responsiveness to the Ca2+ channel activator Bay K 8644 was increased. The corresponding responses in thyroxine-treated animals could not be examined because of prominent arrhythmic activity. As with papillary muscles the sensitivity of left atria to isoproterenol was decreased after treatment with propylthiouracil, with geometric mean EC50 values increasing from 3.21 x 10(-9) mol/l to 89.4 x 10(-9) mol/l.(ABSTRACT TRUNCATED AT 250 WORDS)
Hawthorn
M H
MH
Department of Biochemical Pharmacology, School of Pharmacy, State University of New York, Buffalo 14260.
Gengo
P
P
Wei
X Y
XY
Rutledge
A
A
Moran
J F
JF
Gallant
S
S
Triggle
D J
DJ
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000818:Animals; D006980:Hyperthyroidism / Q000378:metabolism; D066298:In Vitro Techniques; D020120:Iodocyanopindolol; D007473:Ion Channels / Q000378:metabolism*; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D009568:Nitrendipine; D009929:Organ Size / Q000187:drug effects; D010210:Papillary Muscles / Q000187:drug effects / Q000378:metabolism; D010869:Pindolol / Q000031:analogs & derivatives; D051381:Rats; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D013623:Tail / Q000098:blood supply; D013961:Thyroid Gland / Q000187:drug effects / Q000502:physiology*; D013974:Thyroxine / Q000378:metabolism
D007473:Ion Channels; D011943:Receptors, Adrenergic, beta; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D020120:Iodocyanopindolol; D009568:Nitrendipine; D010869:Pindolol; D007545:Isoproterenol; D013974:Thyroxine