Multiple drug classes and hyperosmolarity alter binding of muscarinic drugs to mesothelial cells in vitro.
Mesothelial cells in vitro exhibited binding sites for L-quinuclidinyl[phenyl-4-3H]-benzilate ([3H]-QNB), but not [3H]-N-methylscopolamine (NMS), a cell-impermeable ligand. [3H]-QNB binding demonstrated a biphasic pattern of binding in living cells: a maximum after 15 min at 37 degrees C was followed by a decrease out to 90 min. [3H]-QNB binding was blocked by increasing concentrations of atropine; WIN35428 and GBR12909, dopamine transport inhibitors also decreased binding. Pretreatment of cells for 18 hours with atropine, QNB, or WIN35428 resulted in enhanced [3H]-QNB binding, but coexposure to cycloheximide blocked this increase. Hyperosmolarity caused by NaCl or mannitol decreased binding of [3H]-QNB to living cells. Thus rabbit peritoneal mesothelial cells possess binding sites for [3H]-QNB that are influenced by other drugs and osmolarity.
Basic Sciences University of Illinois College of Medicine at Peoria, USA.
J T
JT
Hjelle
A K
AK
Ho
M A
MA
Miller-Hjelle
M
M
Reith
K R
KR
Steidley
R
R
Duffield
T
T
Butler
J W
JW
Dobbie
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002478:Cells, Cultured; D003042:Cocaine / Q000031:analogs & derivatives / Q000494:pharmacology; D003513:Cycloheximide / Q000494:pharmacology; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004848:Epithelium / Q000378:metabolism; D008353:Mannitol / Q000494:pharmacology; D018727:Muscarinic Antagonists / Q000378:metabolism; D019832:N-Methylscopolamine; D009994:Osmolar Concentration; D010276:Parasympatholytics / Q000378:metabolism; D010537:Peritoneum / Q000378:metabolism*; D010879:Piperazines / Q000494:pharmacology; D011813:Quinuclidinyl Benzilate / Q000378:metabolism; D011817:Rabbits; D011976:Receptors, Muscarinic / Q000187:drug effects* / Q000378:metabolism*; D012602:Scopolamine Derivatives / Q000378:metabolism; D012965:Sodium Chloride / Q000494:pharmacology
D018765:Dopamine Uptake Inhibitors; D018727:Muscarinic Antagonists; D010276:Parasympatholytics; D010879:Piperazines; D011976:Receptors, Muscarinic; D012602:Scopolamine Derivatives; D008353:Mannitol; D012965:Sodium Chloride; C021279:(1R-(exo,exo))-3-(4-fluorophenyl)-8-methyl-8- azabicyclo(3.2.1)octane-2-carboxylic acid, methyl ester; D011813:Quinuclidinyl Benzilate; D001285:Atropine; C043425:vanoxerine; D003513:Cycloheximide; D003042:Cocaine; D019832:N-Methylscopolamine