5-HT1D receptors in guinea-pig and pigeon brain. Radioligand binding and biochemical studies.
The characteristics of high affinity [3H]5-HT (5-hydroxytryptamine) binding to non 5-HT1A non 5-HT1C sites were examined in crude membranes prepared from different regions of guinea-pig and pigeon brains. The coupling of these sites to adenylate cyclase was examined, and its pharmacological profile investigated. In the presence of 100 nmol/l 8-OH-DPAT (8-hydroxy-2-(di-n-propylamino)tetralin) and 100 nmol/l mesulergine, [3H]5-HT labelled with nanomolar affinity an apparently homogeneous population of recognition sites in guinea-pig and pigeon brain membranes. The rank order of affinities of agonists and antagonists (5-CT (5-carboxamidotryptamine) greater than 5-HT greater than RU 24969 (5-methoxy-3-(1,2,3,6-tetrahydro-4- pyridinyl)-1H indole succinate) greater than yohimbine greater than or equal to rauwolscine greater than DP-5-CT (N,N dipropyl-5-carboxamidotryptamine) greater than or equal to mianserin greater than 8-OH-DPAT greater than mesulergine greater than SDZ 21-009 ((+/-)-4(3-tert-butyl-amino-2-hydroxypropoxy)-indol-2 carbonic acid isopropyl ester) greater than (-)propranolol), as well as their individual pKD values, were very similar to those at porcine caudate 5-HT1D sites and clearly different from those at rat cortex 5-HT1B sites. In the substantia nigra of the guinea-pig the 5-HT receptor-mediated inhibition of forskolin-stimulated adenylate cyclase had a pharmacological profile fully comparable to that of 5-HT1D binding sites (5-CT greater than 5-HT greater than yohimbine greater than RU 24969 greater than 8-OH-DPAT greater than SDZ 21-009 = isamoltane greater than (-)pindolol greater than (-)propranolol).(ABSTRACT TRUNCATED AT 250 WORDS)
Waeber
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C
Preclinical Research, Sandoz Ltd., Basel, Switzerland.
Schoeffter
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Palacios
J M
JM
Hoyer
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D
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000067956:Adenylyl Cyclase Inhibitors; D000818:Animals; D001345:Autoradiography; D001665:Binding Sites; D001921:Brain / Q000648:ultrastructure*; D002417:Cattle; D010856:Columbidae; D005260:Female; D006168:Guinea Pigs; D008297:Male; D051381:Rats; D011985:Receptors, Serotonin / Q000145:classification / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism / Q000494:pharmacology; D013378:Substantia Nigra / Q000201:enzymology; D013764:Tetrahydronaphthalenes / Q000378:metabolism; D014316:Tritium
D000067956:Adenylyl Cyclase Inhibitors; D011985:Receptors, Serotonin; D013764:Tetrahydronaphthalenes; D014316:Tritium; D012701:Serotonin; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin