3H-spiroperidol bound in a saturable, stereospecifically displaceable manner to homogenates of bovine retina. Scatchard analysis of saturation experiments showed a KD of 1.35 nM and a density of binding sites of 107 fmoles · mg protein-1. Stereospecifically displaceable binding was pH and temperature dependent and linear with tissue concentration. Spiroperidol, pimozide, haloperidol and d-butaclamol were the most potent compounds in drug displacement curves (8.74 > pIC50 > 7.61 M). Other neuroleptics such as cisflupenthixol, fluphenazine, clozapine, chlorpromazine and pipamperone, were one order of magnitude less potent. Among dopamine agonists, apomorphine (pIC50 = 7.08 ± 0.19 M) was about 50 times more potent than dopamine itself, epinine and ADTN. Serotonin, α- and ß-adrenergic receptors agonists and antagonists were inactive. These results indicate that the sites labelled by 3H-spiroperidol in retina are dopaminergic; moreover the rank order of various antagonists and agonists observed in displacement curves suggests that this preparation could also provide a useful tool to reveal the selective affinity of drugs for the CNS dopamine receptor linked to the enzyme adenylylcyclase (D1-receptors).
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)
- Pharmacology, Toxicology and Pharmaceutics(all)