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5-Hydroxytryptamine(1A) receptor-stimulated [(35)S]GTPgammaS binding in rat brain: absence of regional differences in coupling efficiency.
J Pharmacol Exp Ther. 2000 Feb; 292(2):684-91.JP

Abstract

In hippocampal membranes, the selective 5-hydroxytryptamine (5-HT(1A)) receptor agonists 8-hydroxy-dipropylaminotetralin (8-OH-DPAT) and N,N-dipropyl-5-carboxamidotryptamine (N,N-DP-5-CT) stimulated guanosine-5'-O-(3-thio)triphosphate ([(35)S]GTPgammaS) binding by 130 to 140%; binding stimulated by nonselective agonists (5-HT and 5-CT) was approximately 30% greater. However, the selective 5-HT(1A) receptor antagonist N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-2-pyridinyl-cyclohex anecarboxamide (WAY100,635) completely abolished the increases produced by 8-OH-DPAT and N,N-DP-5-CT but only eliminated 70% of that elicited by 5-CT. The rank potency order of the tested agonists was identical with their rank order of affinity for 5-HT(1A) receptors [5-CT congruent with N,N-DP-5-CT > R-(+)-8-OH-DPAT > 5-HT > ipsapirone]. Racemic 8-OH-DPAT and the partial agonist ipsapirone exhibited lower intrinsic activity than R-(+)-8-OH-DPAT. R-(+)-8-OH-DPAT also stimulated [(35)S]GTPgammaS binding in cortex, but not in striatum, which lacks 5-HT(1A) receptors. Partial irreversible inactivation of 5-HT(1A) receptors, in vitro with phenoxybenzamine (0.3 or 1 microM) or in vivo with N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (1 mg/kg), reduced the maximal response produced by R-(+)-8-OH-DPAT but did not alter its EC(50). In autoradiographic sections, R-(+)-8-OH-DPAT stimulated [(35)S]GTPgammaS binding in 5-HT(1A) receptor-rich regions (dorsal hippocampus, 123%; lateral septum, 111%; midhippocampus, 110%; dorsal raphe nucleus, 83%; medial prefrontal cortex, approximately 60%). The EC(50) of R-(+)-8-OH-DPAT did not vary significantly among brain regions (46-96 nM). Partial irreversible blockade of 5-HT(1A) receptors in brain sections (phenoxybenzamine, 10 microM) reduced the maximal response without altering the EC(50) in both the hippocampus and dorsal raphe. Despite prior evidence that dorsal raphe somatodendritic 5-HT(1A) autoreceptors exhibit high receptor/effector coupling efficiency (receptor reserve) compared with postsynaptic receptors in hippocampus, there was no evidence of a difference at the level of receptor/G protein coupling.

Authors+Show Affiliations

Millhauser Laboratories, Department of Psychiatry, New York University Medical Center, New York, New York, USA. emanuel.meller@med.nyu.eduNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

10640306

Citation

Meller, E, et al. "5-Hydroxytryptamine(1A) Receptor-stimulated [(35)S]GTPgammaS Binding in Rat Brain: Absence of Regional Differences in Coupling Efficiency." The Journal of Pharmacology and Experimental Therapeutics, vol. 292, no. 2, 2000, pp. 684-91.
Meller E, Li H, Carr KD, et al. 5-Hydroxytryptamine(1A) receptor-stimulated [(35)S]GTPgammaS binding in rat brain: absence of regional differences in coupling efficiency. J Pharmacol Exp Ther. 2000;292(2):684-91.
Meller, E., Li, H., Carr, K. D., & Hiller, J. M. (2000). 5-Hydroxytryptamine(1A) receptor-stimulated [(35)S]GTPgammaS binding in rat brain: absence of regional differences in coupling efficiency. The Journal of Pharmacology and Experimental Therapeutics, 292(2), 684-91.
Meller E, et al. 5-Hydroxytryptamine(1A) Receptor-stimulated [(35)S]GTPgammaS Binding in Rat Brain: Absence of Regional Differences in Coupling Efficiency. J Pharmacol Exp Ther. 2000;292(2):684-91. PubMed PMID: 10640306.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 5-Hydroxytryptamine(1A) receptor-stimulated [(35)S]GTPgammaS binding in rat brain: absence of regional differences in coupling efficiency. AU - Meller,E, AU - Li,H, AU - Carr,K D, AU - Hiller,J M, PY - 2000/1/20/pubmed PY - 2000/2/26/medline PY - 2000/1/20/entrez SP - 684 EP - 91 JF - The Journal of pharmacology and experimental therapeutics JO - J. Pharmacol. Exp. Ther. VL - 292 IS - 2 N2 - In hippocampal membranes, the selective 5-hydroxytryptamine (5-HT(1A)) receptor agonists 8-hydroxy-dipropylaminotetralin (8-OH-DPAT) and N,N-dipropyl-5-carboxamidotryptamine (N,N-DP-5-CT) stimulated guanosine-5'-O-(3-thio)triphosphate ([(35)S]GTPgammaS) binding by 130 to 140%; binding stimulated by nonselective agonists (5-HT and 5-CT) was approximately 30% greater. However, the selective 5-HT(1A) receptor antagonist N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-2-pyridinyl-cyclohex anecarboxamide (WAY100,635) completely abolished the increases produced by 8-OH-DPAT and N,N-DP-5-CT but only eliminated 70% of that elicited by 5-CT. The rank potency order of the tested agonists was identical with their rank order of affinity for 5-HT(1A) receptors [5-CT congruent with N,N-DP-5-CT > R-(+)-8-OH-DPAT > 5-HT > ipsapirone]. Racemic 8-OH-DPAT and the partial agonist ipsapirone exhibited lower intrinsic activity than R-(+)-8-OH-DPAT. R-(+)-8-OH-DPAT also stimulated [(35)S]GTPgammaS binding in cortex, but not in striatum, which lacks 5-HT(1A) receptors. Partial irreversible inactivation of 5-HT(1A) receptors, in vitro with phenoxybenzamine (0.3 or 1 microM) or in vivo with N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (1 mg/kg), reduced the maximal response produced by R-(+)-8-OH-DPAT but did not alter its EC(50). In autoradiographic sections, R-(+)-8-OH-DPAT stimulated [(35)S]GTPgammaS binding in 5-HT(1A) receptor-rich regions (dorsal hippocampus, 123%; lateral septum, 111%; midhippocampus, 110%; dorsal raphe nucleus, 83%; medial prefrontal cortex, approximately 60%). The EC(50) of R-(+)-8-OH-DPAT did not vary significantly among brain regions (46-96 nM). Partial irreversible blockade of 5-HT(1A) receptors in brain sections (phenoxybenzamine, 10 microM) reduced the maximal response without altering the EC(50) in both the hippocampus and dorsal raphe. Despite prior evidence that dorsal raphe somatodendritic 5-HT(1A) autoreceptors exhibit high receptor/effector coupling efficiency (receptor reserve) compared with postsynaptic receptors in hippocampus, there was no evidence of a difference at the level of receptor/G protein coupling. SN - 0022-3565 UR - https://www.unboundmedicine.com/medline/citation/10640306/5_Hydroxytryptamine_1A__receptor_stimulated_[_35_S]GTPgammaS_binding_in_rat_brain:_absence_of_regional_differences_in_coupling_efficiency_ L2 - http://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=10640306 DB - PRIME DP - Unbound Medicine ER -