TY - JOUR
T1 - Pharmacological differentiation of presynaptic M1 muscarinic receptors modulating acetylcholine release from postsynaptic muscarinic receptors in guinea-pig ileum
AU - Kawashima, Koichiro
AU - Fujimoto, Kazuko
AU - Suzuki, Takeshi
AU - Oohata, Hisayo
N1 - Funding Information:
Dose-dependednetc reasein spontaneouAsC h reThe resultso f the presents tudyd emonstratteh at leasew as observedin the presencoe f AF-DX 116 at presynapticm uscarinicr eceptorsm odulatingA Ch concentrationbse tween0 .1 and 100g M. A signifi-release are distinct from postsynapticm uscarinic cant decreasew as observeda t concentrationosf receptorsi nvolvedin the contractiler esponseo f 10 and 100/tM (P<0.05 and 0.01, respectively). smooth musclei n guinea-pigil eum.T elenzepinea, Electricallye vokedACh releasew as not affected selectivMe ~m uscariniacn tagonis(Et ltzee t al., 1985), by AF-DX 116 at lower concentrationsb,u t was causeda n increasein electricalleyv okedA Ch release decreasedsi gnificantlya t the highestc oncentrationa t a concentratiotnh at was 100-foldl ess than that tested( 100gM) (P < 0.01) (Fig. 2). The peak con-decreasingth e contractilere sponset o endogenous tractile responset o electricals timulationw as sup-ACh releasedb y electricasl timulationI.n our pre-presseds ignificantlbyy the drug at concentrationosf vious study, pirenzepinea, selectiveM ~ muscarinic 10 and 100/~M( P < 0.01) (Fig. 2). antagonis(tH ammera nd Giachetti,1 982),showed about 100-foldh ighera ffinityf or presynaptimc us-selectivitfyorpostsynaptimcuscarinicreceptorisn-carinic receptorsth an for postsynaptimc uscarinic volved in smooth musclecontractionand showed receptorsw, hile a less than 10-fold differencew as substantiallnyo affinity for presynaptiMcj mus-observeidn thec oncentratioonfs a tropineef fectivein carinic receptors, indicating a possibility that causingin hibitiono f the pre-and postsynaptmicu s-( - )NMS can be usedasan ileal specificpostsynaptic carinicr eceptor(sK awashimaet al., 1988).B asedo n muscarinicantagonistT.hesefindings provide evi-the presenta nd previousd atafrom our laboratory dencethatpre-andp ostsynaptmicuscarinirceceptors and recentr eportby Schuurkese t al. (1988),p rein longitudinaml usclestripsof guinea-piigleumcan synapticm uscarinirce ceptorisn volvedin the modu-be pharmacologicadlliyfferentiatebdytelenzepinoer lation of ACh releasec an be classifieda s the M~ pirenzepinea,ndby (-)NMS. subtypein longitudinaml uscles tripsof guinea-pig ileum.I n additiond, atao btainedin the presenat nd previouss tudiesd emonstratteh at both telenzepine Grant No. 62570995fr om the Ministry of Education, Acknowledgement--This work was supportedin part by M~ muscarinirce ceptorasn dare valuablep harmaco-and pirenzepinhea vehigh selectivitfyo r presynaptic Sciencea ndC ulture,J apanand a Grant from Mitsubishi
PY - 1990
Y1 - 1990
N2 - 1. 1. Effects of three muscarinic antagonists on electrically evoked ACh release and contractile response were investigated in longitudinal muscle strips of guinea-pig ileum suspended in an organ-bath and superfused with Krebs solution. ACh release was determined by a specific radioimmunoassay. 2. 2. Telenzepine, a selective M1 muscarinic antagonist, increased the ACh release at a concentration of 100-fold less than that inhibiting the contractile response (10 vs 1000 nM). 3. 3. AF-DX 116, a cardioselective M2 muscarinic antagonist, inhibited the contractile response at 10 μM, but did not affect the ACh release at this concentration. 4. 4. (-)N-Methylscopolamine (NMS) did not affect the ACh release, but inhibited the contractile response at all concentrations tested (1-1000 nM), indicating (-)NMS can be used as an ileal specific postsynaptic muscarinic antagonist. 5. 5. These data demonstrate that presynaptic muscarinic receptors modulating ACh release are distinct from postsynaptic ones involved in the contractile response and can be classified as M1 subtype.
AB - 1. 1. Effects of three muscarinic antagonists on electrically evoked ACh release and contractile response were investigated in longitudinal muscle strips of guinea-pig ileum suspended in an organ-bath and superfused with Krebs solution. ACh release was determined by a specific radioimmunoassay. 2. 2. Telenzepine, a selective M1 muscarinic antagonist, increased the ACh release at a concentration of 100-fold less than that inhibiting the contractile response (10 vs 1000 nM). 3. 3. AF-DX 116, a cardioselective M2 muscarinic antagonist, inhibited the contractile response at 10 μM, but did not affect the ACh release at this concentration. 4. 4. (-)N-Methylscopolamine (NMS) did not affect the ACh release, but inhibited the contractile response at all concentrations tested (1-1000 nM), indicating (-)NMS can be used as an ileal specific postsynaptic muscarinic antagonist. 5. 5. These data demonstrate that presynaptic muscarinic receptors modulating ACh release are distinct from postsynaptic ones involved in the contractile response and can be classified as M1 subtype.
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U2 - 10.1016/0306-3623(90)90588-D
DO - 10.1016/0306-3623(90)90588-D
M3 - Article
C2 - 2298386
AN - SCOPUS:0025058664
SN - 1537-1891
VL - 21
SP - 17
EP - 21
JO - Vascular Pharmacology
JF - Vascular Pharmacology
IS - 1
ER -