Identification and characterization of muscarinic receptors in cultured human pancreatic carcinoma cells.
Five human pancreatic carcinoma cell lines were screened for the presence of muscarinic cholinergic receptors (mAChRs), using [3H]N-methylscopolamine ([3H]NMS). T3M4 and COLO-357 cells exhibited specific, high-affinity binding to mAChRs. A small amount of [3H]NMS also bound in PANCI and ASPC-I cells, but not in MIA PaCa-2 cells. Atropine, pirenzepine (PZ), and 11-[[2-[(diethylamino) methyly]-1-piperidinyl] acetyl]-5, 11-dihydro-6H-pyrido-[2, 3-b] [1, 4] benzodiazepine-6-one (AF-DX 116) inhibited [3H]NMS binding and carbachol-mediated [3H]inositol monophosphate formation in both T3M4 and COLO-357 cells. The order of inhibition was: atropine greater than PZ greater than AF-DX 116. Carbachol did not alter [3H]inositol monophosphate formation in the other cell lines. These findings suggest that the mAChRs expressed in some human pancreatic cancer cells exhibit the pharmacologic characteristics of a muscarinic receptor subtype with an intermediate affinity for PZ and a lower affinity for AF-DX 116 and are functionally coupled to activation of phospholipid hydrolysis.
Ackerman
M S
MS
Department of Internal Medicine, University of Arizona College of Medicine, Tucson.
Roeske
W R
WR
Heck
R J
RJ
Korc
M
M
D001285:Atropine / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D002460:Cell Line; D006801:Humans; D007295:Inositol Phosphates / Q000378:metabolism; D007700:Kinetics; D019832:N-Methylscopolamine; D010190:Pancreatic Neoplasms / Q000378:metabolism*; D010276:Parasympatholytics / Q000378:metabolism; D010890:Pirenzepine / Q000494:pharmacology; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000378:metabolism*; D012602:Scopolamine Derivatives / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000378:metabolism*
D007295:Inositol Phosphates; D010276:Parasympatholytics; D011976:Receptors, Muscarinic; D012602:Scopolamine Derivatives; D010890:Pirenzepine; D001285:Atropine; D002217:Carbachol; D019832:N-Methylscopolamine