Dihydropyridine Ca/sup + +/ channel agonists enhance /sup 45/Ca/sup + +/ uptake by rabbit aortic smooth muscle cells (RASMC) at 15-50 mM K/sup +/. Nifedipine and D-600 inhibit such effects
RASMC were prepared, subcultured to passage number22 and characterized morphologically and for /sup 45/Ca/sup + +/ uptake. The initial rate of /sup 45/Ca/sup + +/ uptake in 50 mM K/sup +/ was three times the rate in 5 mM K/sup +/. Steady state /sup 45/Ca/sup + +/ uptake increased with K/sup +/ concentration in a dose-dependent manner. Threshold was at approx. 15 mM K/sup +/. At 25-50 mM K/sup +/ the maximum K/sup +/-induced Ca/sup + +/ uptake was 1.3 nmol Ca/sup + +//mg protein or 0.6 nmol Ca/sup + +//10/sup 6/ cells. The three dihydropyridine agonists (+/-) Bay K 8644, (+/-) CGP 28392 and (+) 202-791 enhanced the /sup 45/Ca/sup + +/ uptake at K/sup +/ greater than or equal to 15 nM. At the /sup 45/Ca/sup + +/ uptake threshold of 15 mM each agonist potentiated /sup 45/Ca/sup + +/ uptake in a dose-dependent manner. Responses were antagonized competitively by nife-dipine and non-competitively by (+/-) D-600. The (-) 202-791 inhibited K/sup +/-induced /sup 45/Ca/sup + +/ uptake (IC/sub 50/ = 4.0 x 10/sup -9/ M). Based on the agreement with literature data on contraction, electrophysiological and /sup 45/Ca/sup + +/ uptake studies using intact vascular tissues, it is concluded that the RASMC possess voltage-dependent Ca/sup + +/ channels functionally similar to intact vascular muscle. These cells are a suitable model system for pharmacological studies of Ca/sup + +/ channels and for characterization of Ca/sup + +/ channel modulators.
- Research Organization:
- G.D. Searle and Co., Skokie, IL
- OSTI ID:
- 5508395
- Report Number(s):
- CONF-8604222-; TRN: 86-026602
- Journal Information:
- Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States), Vol. 45:3; Conference: 70. annual meeting of the Federation of American Society for Experimental Biology, St. Louis, MO, USA, 13 Apr 1986
- Country of Publication:
- United States
- Language:
- English
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