Functional characteristics of heterologously expressed 5-HT receptors

Gerhardt, C.C.; Heerikhuizen, Harm van

doi:10.1016/s0014-2999(97)01115-1

Cited by 162 publications

(127 citation statements)

References 128 publications

Supporting

Mentioning

120

Contrasting

Unclassified

Order By: Relevance

“…1 5HT 1A receptor stimulation does not release endothelium-derived relaxing factor and increase cAMP, of which both substances relax smooth muscles. 1 Therefore, the stimulation of 5HT 1A receptor results in CCP contraction. The efficacy of WAY100635 was apparently reversed between the concentrations of 1 and 10 mM.…”

Section: Discussionmentioning

confidence: 99%

“…Serotonin (5-hydroxytryptamine: 5HT) receptors are classified into seven different subtypes (5HT 1,2,3,4,5,6,7 ), and 5HT 1 and 5HT 2 receptors are, respectively, subdivided into five subtypes (5HT 1A, 1B, 1D, 1E, 1F ) and into three subtypes (5HT 2A, 2B, 2C ). 1 Fenfluramine (5HT-releasing agent) and 5-hydroxytryptophan (5HT precursor) with the peripheral decarboxylase inhibitor induce the penile erection through the central nervous system in rats.…”

Section: Introductionmentioning

confidence: 99%

“…1 Fenfluramine (5HT-releasing agent) and 5-hydroxytryptophan (5HT precursor) with the peripheral decarboxylase inhibitor induce the penile erection through the central nervous system in rats. 2 This penile erection is induced by stimulation of the 5HT 1C receptor, 3 which is now recognized as 5HT 2C receptor.…”

Section: Introductionmentioning

confidence: 99%

“…2 This penile erection is induced by stimulation of the 5HT 1C receptor, 3 which is now recognized as 5HT 2C receptor. 1 The stimulation of 5HT 1A or 5HT 2 receptor by administration of 5HT agonists inhibits the penile erection in rats. 3 It is unknown whether peripheral administration of 5HT agonists in vivo shows the penile erection via central and/or peripheral mechanisms.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Responses to serotonin (5HT) in isolated corpus cavernosum penis of rabbit

et al. 2003

View full text Add to dashboard Cite

This study was aimed at determining serotonin (5-hydroxytryptamine: 5HT) receptor subtypes participating in 5HT-induced response in the isolated corpus cavernosum penis (CCP) of rabbits. 5HT contracted the CCP in a concentration-dependent manner. Both WAY100635 (5HT 1A antagonist) and LY53857 (5HT 2 antagonist) concentration-dependently suppressed the 5HT-induced contraction. The suppression of the 5HT-induced contraction by ketanserin (5HT 2A antagonist) was weaker than that by LY53857. LY278584 (5HT 3 antagonist) did not affect the 5HT-induced contraction. SDZ205557 (5HT 4 antagonist) showed a tendency to potentiate the 5HT-induced contraction. The above results suggest that 5HT 1A and 5HT 2 receptor subtypes partially participate in the contractile response to 5HT in rabbit CCP, and the potentiation by SDZ205557 of the 5HT-induced contraction implies the existence of dual contractile and relaxing responses to 5HT via 5HT 1 and 5HT 2 , and 5HT 4 receptors, respectively. The relaxing response to 5HT 4 receptor stimulation may be masked by 5HT-induced contraction.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Responses to serotonin (5HT) in isolated corpus cavernosum penis of rabbit

et al. 2003

View full text Add to dashboard Cite

show abstract

“…The 5-HT2 class of receptors, via G,,,, G proteins, activate phospholipase C, leading to the hydrolysis of PIS and subsequent mobilization of intracellular Ca2+ (for reviews, see Gerhardt and van Heerikhuizen, 1997;Roth et al, 1998). The IAs (relative efficacies) of agonists in promoting the hydrolysis of PIS were determined with adherent whole cells that had low receptor reserve.…”

Section: Discussionmentioning

confidence: 99%

High‐Affinity Agonist Binding Correlates with Efficacy (Intrinsic Activity) at the Human Serotonin 5‐HT_2A and 5‐HT_2C Receptors: Evidence Favoring the Ternary Complex and Two‐State Models of Agonist Action

Fitzgerald

Conklin

Krause

et al. 1999

Journal of Neurochemistry

View full text Add to dashboard Cite

Many modern models of receptor-G protein function assume that there is a direct relationship between high-affinity agonist binding and efficacy. The validity of this assumption has been recently questioned for the serotonin 5-HT2, receptor. We examined the intrinsic activities of various ligands in activating phosphoinositide hydrolysis and measured their respective binding affinities to the high-and low-affinity states of the 5-HTzC (VNV isoform) and 5-HT2, receptors. Ligand binding affinities for the high-affinity state of the receptors were determined using 1 -(4-[1251]iodo-2,5-dimethoxyphenyl)-2-aminopropane, whereas rH]mesulergine and N-rH]-methylspiperone were used, in the presence of excess guanine nucleotide [guanosine 5'-0-(3-thiotriphosphate)], to define binding to the low-affinity state of the 5-HTzc and 5-HT2, receptors, respectively. Antagonists labeled the high-and low-affinity states of each receptor with comparable affinities. Previously identified inverse agonists of the 5-HT2, receptor behaved as silent antagonists in our systems even when the receptor was overexpressed at a relatively high density. In contrast, the ability of agonists to bind differentially to the high-and low-affinity states of the 5-HT2, and 5-HT2, receptors was highly correlated (r2 = 0.86 and 0.96, respectively) with their intrinsic activities. These data suggest that high-affinity agonist states can account for agonist efficacy at human 5-HTz, or 5-HTz, receptors without the need for considering additional transition or active states of the receptor-ligand complex. The procedure described herein may expedite drug discovery efforts by predicting intrinsic activities of ligands solely from ligand binding assays.

show abstract

Serotonergic regulation of blood glucose levels in the crayfish,Procambarus clarkii: Site of action and receptor characterization

et al. 2000

View full text Add to dashboard Cite

The present study investigated the site of action of 5‐hydroxytryptamine (5‐HT) and pharmacologically characterized the receptors involved in regulating blood glucose levels in the crayfish, Procambarus clarkii. Injection of 5‐HT into intact animals increased glucose levels in a dose‐dependent manner. In contrast, 5‐HT failed to elicit a hyperglycemic response in eyestalk‐ablated animals. Effects of several 5‐HT receptor agonists and antagonists were examined. 5‐CT, oxymetazoline (both 5‐HT1 receptor agonists) and α‐methyl‐5‐HT (a 5‐HT2 receptor agonist), but not 1‐phenylbiguanide, m‐CPBG (both 5‐HT3 receptor agonists), or RS 67333 (a 5‐HT4 receptor agonist), induced hyperglycemic responses in a dose‐dependent manner. In addition, 8‐OH‐DPAT (a 5‐HT1A receptor agonist), L‐694,247 (a 5‐HT1B/1D receptor agonist), and DOI (a 5‐HT2A receptor agonist) were effective in significantly increasing the glucose levels, whereas both BW 723C86 (a 5‐HT2B receptor agonist) and m‐CPP (a 5‐HT2C receptor agonist) were ineffective. Finally, ketanserin (a 5‐HT2A receptor antagonist), but not p‐MPPF (a 5‐HT1A receptor antagonist), GR 55562 (a 5‐HT1B/1D receptor antagonist), SB 206553 (a 5‐HT2B/2C receptor antagonist), or tropisetron (a 5‐HT3 receptor antagonist), was able to block 5‐HT‐induced hyperglycemia. The combined results support the hypothesis that 5‐HT exerts its hyperglycemic effect by enhancing the release of hyperglycemic factor(s) from the eyestalks, and suggest that 5 HT‐induced hyperglycemia is mediated by 5‐HT1‐ and 5‐HT2‐like receptors. J. Exp. Zool. 286:596–605, 2000. © 2000 Wiley‐Liss, Inc.

show abstract

Functional characteristics of heterologously expressed 5-HT receptors

Cited by 162 publications

References 128 publications

Responses to serotonin (5HT) in isolated corpus cavernosum penis of rabbit

Responses to serotonin (5HT) in isolated corpus cavernosum penis of rabbit

High‐Affinity Agonist Binding Correlates with Efficacy (Intrinsic Activity) at the Human Serotonin 5‐HT_2A and 5‐HT_2C Receptors: Evidence Favoring the Ternary Complex and Two‐State Models of Agonist Action

Serotonergic regulation of blood glucose levels in the crayfish,Procambarus clarkii: Site of action and receptor characterization

Contact Info

Product

Resources

About

Functional characteristics of heterologously expressed 5-HT receptors

Cited by 162 publications

References 128 publications

Responses to serotonin (5HT) in isolated corpus cavernosum penis of rabbit

Responses to serotonin (5HT) in isolated corpus cavernosum penis of rabbit

High‐Affinity Agonist Binding Correlates with Efficacy (Intrinsic Activity) at the Human Serotonin 5‐HT2A and 5‐HT2C Receptors: Evidence Favoring the Ternary Complex and Two‐State Models of Agonist Action

Serotonergic regulation of blood glucose levels in the crayfish,Procambarus clarkii: Site of action and receptor characterization

Contact Info

Product

Resources

About

High‐Affinity Agonist Binding Correlates with Efficacy (Intrinsic Activity) at the Human Serotonin 5‐HT_2A and 5‐HT_2C Receptors: Evidence Favoring the Ternary Complex and Two‐State Models of Agonist Action