Lack of a dopamine autoreceptor selective profile of B-HT 920 in functional in vitro model systems of D2 receptors in rat striatum

B Drukarch, E Schepens, M J Dolleman-Van der Weel, P De Boer, B J Van Vliet, J C Stoof

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Based on the results of in vivo studies, the thiazoloazepine derivative B-HT 920 has been proposed to be a selective agonist of dopamine autoreceptors. In the present study, we investigated the effects of B-HT 920 in two functional in vitro model systems of D2 receptors and compared these effects with the effects of the classical D2 agonist LY 171555. B-HT 920 and LY 171555 concentration dependently inhibited the electrically evoked release of radiolabeled dopamine and acetylcholine and the forskolin-induced stimulation of adenylate cyclase activity in rat striatal tissue slices with comparable efficacies. In striatal tissue slices prepared after 6-hydroxydopamine-induced destruction of dopaminergic terminals, both drugs were still able to inhibit forskolin-stimulated adenylate cyclase activity with a efficacy similar to that in tissue obtained from unlesioned rats. It is concluded that, in vitro, B-HT 920 is an agonist at both presynaptic and 'normosensitive' postsynaptic D2 receptors showing relatively high intrinsic activity.

Original languageEnglish
Pages (from-to)257-69
Number of pages13
JournalEuropean Journal of Pharmacology
Volume187
Issue number2
Publication statusPublished - 9 Oct 1990

Cite this

Drukarch, B., Schepens, E., Dolleman-Van der Weel, M. J., De Boer, P., Van Vliet, B. J., & Stoof, J. C. (1990). Lack of a dopamine autoreceptor selective profile of B-HT 920 in functional in vitro model systems of D2 receptors in rat striatum. European Journal of Pharmacology, 187(2), 257-69.
Drukarch, B ; Schepens, E ; Dolleman-Van der Weel, M J ; De Boer, P ; Van Vliet, B J ; Stoof, J C. / Lack of a dopamine autoreceptor selective profile of B-HT 920 in functional in vitro model systems of D2 receptors in rat striatum. In: European Journal of Pharmacology. 1990 ; Vol. 187, No. 2. pp. 257-69.
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abstract = "Based on the results of in vivo studies, the thiazoloazepine derivative B-HT 920 has been proposed to be a selective agonist of dopamine autoreceptors. In the present study, we investigated the effects of B-HT 920 in two functional in vitro model systems of D2 receptors and compared these effects with the effects of the classical D2 agonist LY 171555. B-HT 920 and LY 171555 concentration dependently inhibited the electrically evoked release of radiolabeled dopamine and acetylcholine and the forskolin-induced stimulation of adenylate cyclase activity in rat striatal tissue slices with comparable efficacies. In striatal tissue slices prepared after 6-hydroxydopamine-induced destruction of dopaminergic terminals, both drugs were still able to inhibit forskolin-stimulated adenylate cyclase activity with a efficacy similar to that in tissue obtained from unlesioned rats. It is concluded that, in vitro, B-HT 920 is an agonist at both presynaptic and 'normosensitive' postsynaptic D2 receptors showing relatively high intrinsic activity.",
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Drukarch, B, Schepens, E, Dolleman-Van der Weel, MJ, De Boer, P, Van Vliet, BJ & Stoof, JC 1990, 'Lack of a dopamine autoreceptor selective profile of B-HT 920 in functional in vitro model systems of D2 receptors in rat striatum' European Journal of Pharmacology, vol. 187, no. 2, pp. 257-69.

Lack of a dopamine autoreceptor selective profile of B-HT 920 in functional in vitro model systems of D2 receptors in rat striatum. / Drukarch, B; Schepens, E; Dolleman-Van der Weel, M J; De Boer, P; Van Vliet, B J; Stoof, J C.

In: European Journal of Pharmacology, Vol. 187, No. 2, 09.10.1990, p. 257-69.

Research output: Contribution to journalArticleAcademicpeer-review

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AU - Drukarch, B

AU - Schepens, E

AU - Dolleman-Van der Weel, M J

AU - De Boer, P

AU - Van Vliet, B J

AU - Stoof, J C

PY - 1990/10/9

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N2 - Based on the results of in vivo studies, the thiazoloazepine derivative B-HT 920 has been proposed to be a selective agonist of dopamine autoreceptors. In the present study, we investigated the effects of B-HT 920 in two functional in vitro model systems of D2 receptors and compared these effects with the effects of the classical D2 agonist LY 171555. B-HT 920 and LY 171555 concentration dependently inhibited the electrically evoked release of radiolabeled dopamine and acetylcholine and the forskolin-induced stimulation of adenylate cyclase activity in rat striatal tissue slices with comparable efficacies. In striatal tissue slices prepared after 6-hydroxydopamine-induced destruction of dopaminergic terminals, both drugs were still able to inhibit forskolin-stimulated adenylate cyclase activity with a efficacy similar to that in tissue obtained from unlesioned rats. It is concluded that, in vitro, B-HT 920 is an agonist at both presynaptic and 'normosensitive' postsynaptic D2 receptors showing relatively high intrinsic activity.

AB - Based on the results of in vivo studies, the thiazoloazepine derivative B-HT 920 has been proposed to be a selective agonist of dopamine autoreceptors. In the present study, we investigated the effects of B-HT 920 in two functional in vitro model systems of D2 receptors and compared these effects with the effects of the classical D2 agonist LY 171555. B-HT 920 and LY 171555 concentration dependently inhibited the electrically evoked release of radiolabeled dopamine and acetylcholine and the forskolin-induced stimulation of adenylate cyclase activity in rat striatal tissue slices with comparable efficacies. In striatal tissue slices prepared after 6-hydroxydopamine-induced destruction of dopaminergic terminals, both drugs were still able to inhibit forskolin-stimulated adenylate cyclase activity with a efficacy similar to that in tissue obtained from unlesioned rats. It is concluded that, in vitro, B-HT 920 is an agonist at both presynaptic and 'normosensitive' postsynaptic D2 receptors showing relatively high intrinsic activity.

KW - Adenylyl Cyclases

KW - Animals

KW - Azepines

KW - Colforsin

KW - Corpus Striatum

KW - Dopamine Agents

KW - Ergolines

KW - Hydroxydopamines

KW - In Vitro Techniques

KW - Male

KW - Neurotransmitter Agents

KW - Oxidopamine

KW - Quinpirole

KW - Rats

KW - Rats, Inbred Strains

KW - Receptors, Dopamine

KW - Stereoisomerism

KW - Sympathectomy, Chemical

KW - Journal Article

M3 - Article

VL - 187

SP - 257

EP - 269

JO - European Journal of Pharmacology

JF - European Journal of Pharmacology

SN - 0014-2999

IS - 2

ER -