text: Pharmacological characterization of unique prazosin-binding sites in human kidney.
  In human kidney, we found unique prazosin-binding sites that were insensitive to phentolamine and were thus unlikely to be alpha(1)-adrenoceptors. As the binding of [(3)H]prazosin to phentolamine-insensitive sites was prevented by 100 microM guanabenz, the insensitive sites were evaluated by subtracting [(3)H]prazosin binding in the presence of 100 microM guanabenz from that in the presence of 10 microM phentolamine. [(3)H]Prazosin bound to the phentolamine-insensitive sites monophasically with a high affinity (pK(d); 9.1+/-0.08, n=8), and the B(max) value (814+/-204 fmol mg(-1) protein, n=8) was more than ten times that of the phentolamine-sensitive alpha(1)-adrenoceptor (pK(d)=9.9+/-0.13, B(max)=66+/-23 fmol mg(-1) protein, n=7). The phentolamine-insensitive sites in human kidney were highly sensitive to other quinazoline derivatives such as terazosin and doxazosin. However, other alpha(1)-adrenoceptor antagonists (tamsulosin, WB4101 and corynanthine) did not inhibit the binding at a range of concentrations that generally exhibit alpha(1)-adrenoceptor antagonism, and noradrenaline, rauwolscine and propranolol were without effect on the [(3)H]prazosin binding. On the other hand, ligands for the renal Na(+)-transporter (amiloride and triamterene) and for imidazoline recognition sites (guanabenz, guanfacine and agmatine) displaced the binding of [(3)H]prazosin to phentolamine-insensitive sites at micromolar concentrations. Photoaffinity labeling with [(125)I]iodoarylazidoprazosin showed phentolamine-insensitive labeling at around 100 kDa, a molecular size larger than that of human alpha(1a)- and alpha(1b)-adrenoceptors expressed in 293 cells (50-60 and 70-80 kDa, respectively) on electrophoresis. In contrast, there was no detectable phentolamine-insensitive binding site but were phentolamine-sensitive alpha(1)-adrenoceptors in human liver (pK(d)=10.0+/-0.06, B(max)=44+/-6 fmol mg(-1) protein, n=3). Phentolamine-insensitive prazosin binding sites were also detected in rabbit kidney (approximately 50% of specific binding sites) but were minor in rat kidney (less than 20%). In conclusion, there are unique prazosin-binding sites in human kidney, the pharmacological profiles of which were distinct from those of known adrenoceptors.
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entities.type: CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL GENE-N GENE-N GENE-N GENE-N GENE-N GENE-N GENE-N CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL
entities.text: guanfacine agmatine [(3)H]prazosin phentolamine [(125)I]iodoarylazidoprazosin phentolamine [(3)H]prazosin phentolamine phentolamine phentolamine noradrenaline Phentolamine prazosin prazosin guanabenz [(3)H]prazosin prazosin guanabenz phentolamine [(3)H]Prazosin phentolamine rauwolscine phentolamine phentolamine phentolamine quinazoline terazosin doxazosin tamsulosin WB4101 corynanthine prazosin propranolol alpha(1)-adrenoceptor Na(+)-transporter alpha(1)-adrenoceptors human alpha(1a)- and alpha(1b)-adrenoceptors alpha(1)-adrenoceptors alpha(1)-adrenoceptor alpha(1)-adrenoceptor [(3)H]prazosin Na(+) amiloride triamterene imidazoline guanabenz