Alterations of α1-adrenoceptor subtypes in the hearts of thyroxine-treated rats

• Published in: European journal of pharmacology 1995-12, Vol.294 (2), p.593-599
• Main Authors: Han, Chide, Yu, Gengsheng, Zhang, Youyi, Xu, Kaimin, Qu, Peng, Dong, Erdan
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Endocrinopathies; Heart; Medical sciences; mRNA; Non tumoral diseases. Target tissue resistance. Benign neoplasms; Thyroid. Thyroid axis (diseases); Thyroxine treatment; α1-Adrenoceptor, subtype
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/0014-2999(95)00607-9

Alterations in the cardiac α 1-adrenoceptor and its subtypes in thyroxine-treated rats were studied by means of radioligand binding assays, measurement of contractile response and reverse transcription-polymerase chain reaction (RT-PCR). The results showed that in thyroxine-treated rats the cardiac α 1-adrenoceptor density ( B max) was reduced from 51.6 ± 6.0 fmol/mg in control to 40.9 ± 3.7 fmol/mg ( P < 0.01); and the percentage of high affinity sites for 5-methyl-urapidil decreased from 23.3 ± 2.0% in control to 10.8 ± 2.0% in thyroxine-treated rats ( P < 0.05). The data indicated that the high-affinity sites for 5-methyl-urapidil ( α 1A-adrenoceptor) were reduced (from 12.0 to 4.4 fmol/mg), but the low-affinity sites for 5-methyl-urapidil ( α 1B- plus α 1D-adrenoceptor) were not changed from 39.6 to 36.5 fmol/mg). RT-PCR showed that steady-state levels of mRNA for α 1A- and α 1B-adrenoceptors were decreased, while that for α 1D-adrenoceptor was raised in thyroxine-treated rats. In the isolated electrically driven left atria the phenylephrine-induced maximal contractions were reduced from 258 ± 17 mg in control to 188 ± 24 mg in thyroxine-treated rats ( P < 0.05). The pA 2 values of 5-methyl-urapidil were reduced from 8.89 ± 0.36 in control to the hyperthyroidism of 7.87 ± 0.43 in thyroxine-treated rats ( P < 0.05). Chlorethylclonidine preincubation shifted concentration-response curves for phenylephrine to the right and reduced the maximal response to a lesser extent in thyroxine-treated rats than in control rats. Thus we concluded that the total number of cardiac α 1-adrenoceptors is reduced in thyroxine-treated rats. The change is subtype selective, with α 1A- and α 1B-adrenoceptors being reduced in number and α 1D-adrenoceptor being increased.