TY - JOUR
T1 - Identification and characterization of muscarinic receptors in cultured human pancreatic carcinoma cells
AU - Ackerman, Martha S.
AU - Roeske, William R.
AU - Heck, Richard J.
AU - Korc, Murray
N1 - Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 1989/6
Y1 - 1989/6
N2 - Five human pancreatic carcinoma cell lines were screened for the presence of muscarinic cholinergic receptors (mAChRs), using [3H]7V-meth-ylscopolamine ([3H]NMS). T3M4 and COLO-357 cells exhibited specific, high-affinity binding to mAChRs. A small amount of [3H]NMS also bound in PANC-I and ASPC-I cells, but not in MIA PaCa-2 cells. Atropine, pirenzepine (PZ), and ll-[[2-[(diethylamino) methyl]-1-piperidinyl] acetyl]-5, ll-dihydro-6H-pyrido-[2, 3-b][l, 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 > PZ > 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.
AB - Five human pancreatic carcinoma cell lines were screened for the presence of muscarinic cholinergic receptors (mAChRs), using [3H]7V-meth-ylscopolamine ([3H]NMS). T3M4 and COLO-357 cells exhibited specific, high-affinity binding to mAChRs. A small amount of [3H]NMS also bound in PANC-I and ASPC-I cells, but not in MIA PaCa-2 cells. Atropine, pirenzepine (PZ), and ll-[[2-[(diethylamino) methyl]-1-piperidinyl] acetyl]-5, ll-dihydro-6H-pyrido-[2, 3-b][l, 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 > PZ > 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.
KW - Muscarinic receptors
KW - Pancreatic carcinomas
KW - Phospholipid hydrolysis
UR - http://www.scopus.com/inward/record.url?scp=84934741466&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84934741466&partnerID=8YFLogxK
U2 - 10.1097/00006676-198906000-00014
DO - 10.1097/00006676-198906000-00014
M3 - Article
C2 - 2734280
AN - SCOPUS:84934741466
VL - 4
SP - 1
EP - 2
JO - Pancreas
JF - Pancreas
SN - 0885-3177
IS - 3
ER -