Functional and autoradiographic evidence for endothelin 1 receptors on human and rat cardiac myocytes. Comparison with single smooth muscle cells.
This study aimed to determine whether receptors for endothelin were present on the cardiac myocyte as well as on vascular smooth muscle cells. Low- and high-resolution autoradiography was performed using 125I-endothelin 1 on intact rat myocardium and samples of human ventricle obtained from explanted hearts at the time of transplant. In addition to specific binding to the smooth muscle of the blood vessel lumen, there was considerable binding associated with cardiac myocytes. To discover whether there was any functional correlate for this binding, muscle cells were isolated enzymatically from human and rat ventricle and from rat femoral artery, and their contractile characteristics were studied. Single cardiac cells were superfused with physiological saline at 32 degrees C, and their length change was displayed continuously on a chart recorder. Endothelin 1 had a pronounced effect on shortening in both rat and human myocytes. The contraction amplitude was approximately doubled in both cases, from 4.1 +/- 0.8% cell length to 8.1 +/- 1.3% for rat (mean +/- SEM, n = 9, p less than 0.001), and from 2.1 +/- 0.5% to 4.0 +/- 0.5% in human (n = 10, p less than 0.001). In rat, the magnitude of the effect was comparable to that of the alpha-adrenoceptor agonist phenylephrine. The maximum contraction amplitude of the human cells, produced by raising extracellular calcium to greater than 10 mM, was 11.4 +/- 1.1% cell length (n = 9), significantly greater than that produced by endothelin (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
Moody
C J
CJ
National Heart and Lung Institute, London, U.K.
Dashwood
M R
MR
Sykes
R M
RM
Chester
M
M
Jones
S M
SM
Yacoub
M H
MH
Harding
S E
SE
D000818:Animals; D001345:Autoradiography; D001665:Binding Sites; D006652:Histological Techniques; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000032:analysis* / Q000166:cytology / Q000378:metabolism; D009200:Myocardial Contraction; D009206:Myocardium / Q000032:analysis* / Q000166:cytology / Q000378:metabolism; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011956:Receptors, Cell Surface / Q000032:analysis* / Q000378:metabolism; D017466:Receptors, Endothelin
D011956:Receptors, Cell Surface; D017466:Receptors, Endothelin; D010656:Phenylephrine