SPARE CHOLINERGIC RECEPTORS IN THE URINARY-BLADDER

  • 1 January 1982
    • journal article
    • research article
    • Vol. 221  (3) , 598-603
Abstract
The concentration-effect relationships of carbachol were studied for 3 different responses of detrusor muscle of rabbit urinary bladder: the mechanical response, the increase of 45Ca uptake and the displacement of [3H]quinuclidinyl benzilate (QNB) from muscarinic receptors. The EC50 [median effective concentration] for carbachol in production of contractile responses of the detrusor muscle was 0.27 .mu.M. The 45Ca uptake by detrusor muscle strips was studied by the La-residual wash out method. Carbachol increased 45Ca uptake with an EC50 of 12.7 .mu.M. [3H]QNB binding was performed on homogenates of rabbit bladder detrusor muscle. By Scatchard analysis, the receptor density was 47.2 f[femto]mol/mg of protein and the Kd, 0.074 nM. The contractile responses, the 45Ca uptake and the specific [3H]QNB binding were all blocked by atropine and so are taken to represent muscarinic receptor-mediated phenomena. Carbachol displacement of [3H]QNB yielded an EC50 of 135 .mu.M and a Ki [inhibition constant] of 42 .mu.M. Apparently, the mechanical response requires a much lower concentration of carbachol than that needed for stimulating 45Ca uptake or for occupying [3H]QNB binding sites and there appears to be .apprx. a 150-fold muscarinic receptor excess.