TY  - JOUR
A1  - Pfeiffer, A.
A1  - Rochlitz, H.
A1  - Noelke, B.
A1  - Tacke, R.
A1  - Moser, U.
A1  - Mutschler, E.
A1  - Lambrecht, G.
T1  - Muscarinic receptors mediating acid secretion in isolated rat gastric parietal cells are of M3 type
JF  - Gastroenterology
N2  - Five subtypes of muscarinic receptors have been identified by pharmacological and molecular biological methods. The muscarinic receptor subtype mediating acid secretion at the level of the parietal cell was unknown. Therefore, this study was performed to characterize muscarinic receptors on rat gastric parietal cells using the 3 subtype-selective antagonists hexahydrosiladifenidol and silahexocyclium, which have high affinity for glandular M3 subtypes, and AF-DX 116, which has high affinity to cardiac M2 receptors. The affinity of these antagonists was determined by radioligand binding experiments. In addition, their inhibitory potency on carbachol-stimulated inositol phosphate production was investigated. Inhibition of carbachol-stimulated aminopyrine uptake was used as an indirect measure of proton production. Both M3 antagonists, hexahydrosiladifenidol and silahexocyclium, had nanomolar affinities for parietal cell muscarinic receptors and potently antagonized inositol phosphate production with nanomolar Ki values. Silahexocyclium similarly antagonized aminopyrine accumulation while hexahydrosiladifenidol behaved as a noncompetitive antagonist. AF-DX 116 was a low-affinity ligand and a weak competitive antagonist at parietal-cell muscarinic receptors. It was concluded that muscarinic M3 receptors mediate acid secretion probably by activation of the phosphoinositide second messenger system in rat gastric parietal cells.
KW  - hexahydrosiladifenidol
KW  - muscarinic receptors
KW  - parasympatholytics
KW  - radioligand assay
KW  - parasympatholytics/pharmacology
KW  - gastric acid/secretion
KW  - animals
KW  - piperidines/pharmacology
KW  - piperazines/pharmacology
KW  - gastric/secretion parietal cells
KW  - muscarinic/physiology receptors
KW  - muscarinic/drug effects receptors
KW  - rats
KW  - piperidines
KW  - piperazines
KW  - silahexocyclium
Y1  - 1990
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-128337
VL  - 98
IS  - 1
ER  - 
TY  - JOUR
A1  - Jaiswal, Neelam
A1  - Lambrecht, Günter
A1  - Mutschler, Ernst
A1  - Tacke, Reinhold
A1  - Malik, Kafait U.
T1  - Pharmacological characterization of the vascular muscarinic receptors mediating relaxation and contraction in rabbit aorta
JF  - Journal of Pharmacology and Experimental Therapeutics
N2  - Studies were performed in the rabbit aortic rings, precontracted with norepinephrine, to determine the subtype(s) of muscarinic receptors involved in endothelium-dependent relaxation and contraction in the absence of endothelium elicited by cholinergic stimuli. Acetylcholine (ACh) and arecaidine propargyl ester (APE), a M2 and M3 agonist, produced a dose-dependent relaxation and contraction in endothelium-intact and endothelium-denuded rabbit aortic rings, respectively. Both of these responses were blocked by the muscarinic receptor antagonist atropine. M1 selective agonist McN-A-343 [4-[N-(3-chlorophenyl)carbamoyloxy]-2-butinyltrimethylammonium+ ++ chloride] did not produce any effect on the tone of precontracted aortic rings. ACh- and APE-induced relaxation in aortic rings with intact endothelium was selectively blocked by M3 receptor antagonists hexahydrosila-difenidol and p-fluoro-hexahydro-sila-difenidol (pA2 of 7.84 and 7.18) but not by M1 antagonist pirenzepine or M2 receptor antagonists AF-DX 116 [11-(2-[(diethylamino)methyl]- 1-piperidinyl]acetyl)-5, 11-dihydro-6H-pyrido-[2,3-b][1,4]-benzo-diazepin-6-one] and methoctramine. ACh- and APE-induced contraction was inhibited by M2 receptor antagonists AF-DX 116 and methoctramine (pA2 of 7.11 and 6.71) but not by pirenzepine, hexahydro-sila-difenidol or p-fluoro-hexahydro-sila-difenidol. ACh- and APE-induced relaxation or contraction were not altered by nicotinic receptor antagonist hexamethonium or cyclooxygenase inhibitor indomethacin. These data suggest that relaxation elicited by cholinergic stimulin in endothelium-intact aortic rings is mediated via release of endothelium-derived relaxing factor consequent to activation of M3 receptors located on endothelial cells, whereas the contraction in aortic rings denuded of their endothelium is mediated via stimulation of M2 receptors located on smooth muscle cells.
KW  - (4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethylammonium chloride/pharmacology
KW  - acetylcholine
KW  - animals
KW  - antihypertensive agents / pharmacology
KW  - aorta, abdominal / drug effects
KW  - aorta, abdominal / physiology
KW  - aorta, abdominal / ultrastructure
KW  - arecoline/analogs & derivatives
KW  - arecoline
KW  - atropine
KW  - diamines
KW  - endothelium, vascular / drug effects
KW  - endothelium, vascular / physiology
KW  - hexamethonium
KW  - hexamethonium compounds
KW  - indomethacin
KW  - male
KW  - muscarinic antagonists
KW  - muscle contraction
KW  - muscle relaxation
KW  - norepinephrine
KW  - parasympatholytics
KW  - piperidines
KW  - pirenzepine
KW  - rabbits
Y1  - 1991
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-128358
VL  - 258
IS  - 3
ER  -