EFFECT OF AGE ON ENDOTHELIN-1 BINDING-SITES IN RAT CARDIAC VENTRICULAR MEMBRANES

To establish whether the density, affinity, or selectivity of endothelin-1 (ET-1) binding sites in cardiac ventricular membranes varies with age, membranes were harvested from 5- to 7-day-, 20-day-, and 8- to 9-week-old Sprague Dawley rats and labeled with [I-125]ET-1. Selectivity was established by using cold ET-1, ET-2, ET-3, big ET-1, and (+)PN200-110 to inhibit specific binding of [I-125]ET-1. Over the age span studied, selectivity and affinity of the [I-125]ET-1 binding sites was unchanged, but density (B(max)) decreased from 209.7 +/- 18.4 at 5-7 days to 154.0 +/- 8.9 (p < 0.02) at 20 days, and to 89.7 +/- 5.2 (p < 0.01) fmol/mg protein at 8-9 weeks. These age-dependent differences in B(max) were not accompanied by a change in membrane yield and occurred at a time when the specific binding of (+)[H-3]PN200-110 increased.