ISSN:
1432-1912
Keywords:
Calcium antagonist receptors
;
Urinary tract
;
Dihydropyridine
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Summary (+)-[3HPN 200-110 (a dihydropyridine calcium channel antagonist) was utilized to characterize calcium channel binding sites in rabbit bladder dome, bladder base, and urethra. Specific binding of (+)-[3H]PN 200-110 to membrane particulates was saturable, reversible, linear to protein concentration, and of high affinity. The density of (+)-[3H]PN 200-110 binding sites (Bmax values in fmol/mg of protein) and the affinity constants for (+)-[3H]PN 200-110 (KD value in pM) in urethra, bladder dome and bladder base were 64.1 ± 7.8 and 179±31; 21.9±3.0 and 213±36; and 18.8±4.2 and 140±28, respectively. Agonists and antagonists inhibited (+)-[3H]PN 200-110 binding with Ki values in the following rank order: nitrendipine 〈 nifedipine 〈 niguldipine ≪ Bay K 8644 ≪ verapamil. Although carbachol-induced contractile responses were 20–30 times smaller in muscle strips from urethra than from bladder base or bladder dome, KCl-induced contractions were only 3–4 times smaller in urethra than in bladder tissues. Nifedipine inhibited carbachol-induced contractions in urethra, bladder dome, and bladder base by 76%, 64%, and 60%, respectively, and completely inhibited KCl-induced contractions in all three tissues. IC50 values for nifedipine inhibition of both carbachol- and KCl-induced contractions were significantly smaller in urethra than in bladder base or bladder dome. Nitrendipine, niguldipine and verapamil inhibited urethral contractions induced by carbachol and KCl to the same degree as did nifedipine. The IC50 values, obtaines from functional studies, for calcium channel antagonists were in good agreement with Ki values obtained from binding studies. BAY K 8644, a calcium channel agonist, increased both KCl- and carbachol-induced contractions and potentiated CaCl2-induced contractions in K+-depolarizing media in urethra but not in bladder dome or bladder base. Our data indicate that the density of (+)-[3H]PN 200-110 binding sites is higher in the urethra than in the bladder dome or bladder base and that the urethra is functionally more sensitive to dihydropyridine agonists and antagonists than is either the bladder dome or bladder base.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF00164583
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