Alterations of alpha1-adrenoceptor subtypes in the hearts of thyroxine-treated rats.
Alterations in the cardiac alpha1-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 alpha1-adrenoceptor density (Bmax) 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 (alpha1A-adrenoceptor) were reduced (from 12.0 to 4.4 fmol/mg), but the low-affinity sites for 5-methyl-urapidil (alpha1B- plus alpha1D-adrenoceptor) were not changed (from 39.6 to 36.5 fmol/mg). RT-PCR showed that steady-state levels of mRNA for alpha1A- and alpha1B-adrenoceptors were decreased, while that for alpha1D-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 pA2 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 alpha1-adrenoceptors is reduced in thyroxine-treated rats. The change is subtype selective, with alpha1A- and alpha1B-adrenoceptors being reduced in number and alpha1D-adrenoceptor being increased.
Han
C
C
Institute of Vascular Medicine, Third Hospital, Beijing Medical University, People's Republic of China.
Yu
G
G
Zhang
Y
Y
Xu
K
K
Qu
P
P
Dong
E
E
D000818:Animals; D001483:Base Sequence; D006321:Heart / Q000187:drug effects*; D008297:Male; D008969:Molecular Sequence Data; D009200:Myocardial Contraction / Q000187:drug effects; D010627:Phenethylamines / Q000378:metabolism; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D018340:Receptors, Adrenergic, alpha-1 / Q000032:analysis / Q000187:drug effects* / Q000235:genetics; D044024:Tetralones; D013963:Thyroid Hormones / Q000097:blood; D013974:Thyroxine / Q000494:pharmacology*
D010627:Phenethylamines; D012333:RNA, Messenger; D018340:Receptors, Adrenergic, alpha-1; D044024:Tetralones; D013963:Thyroid Hormones; C010652:BE 2254; D013974:Thyroxine