Localization of calcium channels of the L-type in human epicardial arteries: a light microscope autoradiographic study.
The anatomical localization of Ca2+ channels of the L-type was analyzed in sections of the human right and anterior interventricular coronary arteries by using in vitro light microscope autoradiography associated with radioligand binding techniques. [3H]Nicardipine was utilised as a ligand. Binding of the radioligand to sections of the two coronary arteries was time-, temperature- and concentration-dependent. Analysis of binding isotherms revealed a dissociation constant value of about 0.5 nM in the two arteries and maximum binding capacities of 139 +/- 6.4 fmol/mg tissue for the right coronary artery and of 173 +/- 9.5 for the anterior interventricular branch. The pharmacological profile of [3H]nicardipine binding to sections of human coronary arteries was consistent with the labelling of Ca2+ channels of the L-type. Dihydropyridine derivatives were the most powerful competitors of [3H]nicardipine binding, whereas phenylalkylamines, benzothiazepine or non-selective channel modulators were weak competitors or ineffective. Light microscope autoradiography revealed the highest density of [3H]nicardipine binding sites in the tunica media of the coronary arteries. In this layer Ca2+ channels of the L-type are located within smooth muscle cells. A lower accumulation of the radioligand occurred in the tunica adventitia, whereas no specific binding was found in the tunica intima. Study of the localization of Ca2+ channels in sections of human coronary arteries may contribute to a better understanding of the mechanism of the marked coronary dilatory activity elicited by Ca2+ antagonists demonstrable in both in vitro preparations and in vivo.
Ferrante
F
F
Sezione di Anatomia Umana, Università di Camerino, Italy.
Cadoni
A
A
Zaccheo
D
D
Amenta
F
F
D000293:Adolescent; D001345:Autoradiography; D001665:Binding Sites; D002121:Calcium Channel Blockers / Q000378:metabolism; D015220:Calcium Channels / Q000145:classification / Q000378:metabolism*; D003331:Coronary Vessels / Q000033:anatomy & histology / Q000378:metabolism*; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D009529:Nicardipine / Q000378:metabolism; D011869:Radioligand Assay
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D009529:Nicardipine