Biomedical subjects

A Karpf

Publications and source records attributed to A Karpf.

5 recordsLinked to original sources

PubMed1989

[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)

Animals↗

PubMed1989

Competitive interaction of agonists and antagonists with 5-HT3 recognition sites in membranes of neuroblastoma cells labelled with [3H]ICS 205-930.

[3H]ICS 205-930 labelled 5-HT3 recognition sites in membranes prepared from murine neuroblastoma N1E-115 cells. Binding was rapid, reversible, saturable and stereoselective to an apparently homogeneous population of sites. Kinetic studies revealed that agonists and antagonists produced a monophasic dissociation reaction of [3H]ICS 205-930 from its recognition sites. The dissociation rate constant of the radioligand was similar whether the dissociation was induced by an agonist or an antagonist. Competition studies carried out with agonists and antagonists also suggested the presence of a homogeneous population of [3H]ICS 205-930 recognition sites. Competition curves were best fit for a 1 site model. [3H]ICS 205-930 binding sites displayed the pharmacological profile of a 5-HT3 receptor. The interactions of agonists and antagonists with [3H]ICS 205-930 recognition sites were apparently competitive in nature, as demonstrated in kinetic and equilibrium experiments. In saturation experiments carried out with [3H]ICS 205-930 in the presence and the absence of unlabelled agonists and antagonists, apparent Bmax values were not reduced whereas apparent Kd values were increased in the presence of competing ligands. There was a good agreement between apparent pKB values calculated for the competing ligands in saturation experiments and pKd values calculated from competition experiments. The present data demonstrate that [3H]ICS 205-930 labels a homogeneous population of sites at which agonists and antagonists interact competitively.

Animals↗

PubMed1988

[125I]SCH 23982, a 'selective' D-1 receptor antagonist, labels with high affinity 5-HT1C sites in pig choroid plexus.

[125I]SCH 23982, a ligand reported to be very selective for dopamine D-1 receptors, binds with high affinity to membranes of pig choroid plexus (KD = 186 pM, Bmax = 142 fmol/mg protein). Saturation and competition experiments suggested that [125I]SCH 23982 labels a homogeneous population of sites. The rank order for affinity of agonists, 5-HT greater than or equal to DOI (1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane) much greater than dopamine greater than fenoldopam, and antagonists, metergoline greater than mesulergine = mianserin greater than SCH 23390 greater than methiothepin greater than ketanserin greater than fluphenazine much greater than (-)-sulpiride greater than (+)-sulpiride, was compatible with labelling of 5-HT1C receptors by [125I]SCH 23982. It also correlates very significantly with [3H]mesulergine binding to pig choroid plexus membranes. The effects of SCH 23390 and its analogues should not be systematically attributed to an interaction with D-1 receptors.

Animals↗

PubMed1988

Characterisation of 5-HT3 recognition sites in membranes of NG 108-15 neuroblastoma-glioma cells with [3H]ICS 205-930.

1. The binding characteristics of [3H]ICS 205-930, a potent and selective 5-hydroxytryptamine 5-HT3 receptor antagonist, were investigated in membranes prepared from murine neuroblastoma-glioma NG 108-15 cells. 2. [3H]ICS 205-930 bound rapidly, reversibly and stereoselectively to a homogeneous population of high affinity recognition sites: Bmax = 58 +/- 3 fmol/mg protein, pKD = 9.01 +/- 0.08 (n = 11). Non linear regression and Scatchard analysis of saturation data suggested the existence of a single class of [3H]ICS 205-930 recognition sites on NG 108-15 cells. The binding was rapid, stable and reversible. The affinity of [3H]ICS 205-930 determined in kinetic studies was in agreement with that obtained under equilibrium conditions. 3. Competition studies performed with a variety of agonists and antagonists also suggested the presence of a homogeneous population of [3H]ICS 205-930 recognition sites. All competition curves were steep and monophasic and were best fit by a 1 receptor site model. [3H]ICS 205-930 binding sites displayed the pharmacological profile of a 5-HT3 receptor. Potent 5-HT3 receptor antagonists showed nanomolar affinities for [3H]ICS 205-930 binding sites with the following rank order of potency: SDZ 206-830 greater than ICS 205-930 greater than SDZ 206-792 greater than BRL 43694 greater than quipazine greater than BRL 24924 greater than SDZ 210-204 greater than MDL 72222 greater than SDZ 210-205. Metoclopramide, mCP and mianserin showed submicromolar affinity.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

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