[3H]ICS 205-930 labels 5-HT3 recognition sites in membranes of cat and rabbit vagus nerve and superior cervical ganglion.
The binding characteristics of [3H]ICS 205-930, a 5-hydroxytryptamine 5-HT3 receptor antagonist, were investigated in membranes prepared from cat and rabbit vagus nerve (VN) and superior cervical ganglion (SCG). The autoradiographic localisation of 5-HT3 recognition sites was also assessed using [3H]ICS 205-930 in slices from cat medulla oblongata, nodose ganglion and vagus nerve. [3H]ICS 205-930 bound to a homogeneous population of high affinity recognition sites in cat VN: Bmax = 201 +/- 43 fmol/mg protein, pKD = 9.26 +/- 0.17 and SCG: Bmax = 291 +/- 40 fmol/mg, pKD = 9.35 +/- 0.80 (n = 3). Competition experiments performed in membranes from cat VN and SCG with agonists and antagonists suggested the presence of a homogeneous population of [3H]ICS 205-930 recognition sites. Competition curves were steep and monophasic and were best fitted by a 1 receptor site model. The following rank order of affinity for [3H]ICS 205-930 binding sites was observed with antagonists: SDZ 206-830 = ICS 205-930 greater than BRL 43694 greater than SDZ 206-792 greater than quipazine greater than MDL 72222 greater than metoclopramide greater than mCPP and agonists: 2-methyl-5-HT = 5-HT greater than phenylbiguanide. A similar profile was observed for a limited series of compounds in rabbit membranes. Drugs acting at 5-HT1, 5-HT2 and dopamine receptors (domperidone, spiperone and metergoline) showed very low affinities for [3H]ICS 205-930 recognition sites. The sites labelled with [3H]ICS 205-930 in vagus nerve and superior cervical ganglion of both species displayed the pharmacological profile of a 5-HT3 receptor.(ABSTRACT TRUNCATED AT 250 WORDS)
Hoyer
D
D
Preclinical Research, Sandoz Ltd., Basel, Switzerland.
Waeber
C
C
Karpf
A
A
Neijt
H
H
Palacios
J M
JM
D000818:Animals; D001345:Autoradiography; D002415:Cats; D005727:Ganglia, Spinal / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D008526:Medulla Oblongata / Q000187:drug effects / Q000378:metabolism; D008566:Membranes / Q000187:drug effects / Q000378:metabolism; D011817:Rabbits; D011869:Radioligand Assay; D011985:Receptors, Serotonin / Q000187:drug effects*; D012702:Serotonin Antagonists / Q000494:pharmacology*; D000077526:Tropisetron; D014630:Vagus Nerve / Q000187:drug effects / Q000378:metabolism*
D007211:Indoles; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D000077526:Tropisetron