Coupling of an endogenous 5‐HT<sub>1B</sub>‐like receptor to increases in intracellular calcium through a pertussis toxin‐sensitive mechanism in CHO‐K1 cells

Dickenson, John M.; Hill, Stephen J.

doi:10.1111/j.1476-5381.1995.tb15941.x

Cited by 24 publications

(27 citation statements)

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“…Previous studies have demonstrated that activation of both 5-HT 1B and 5-HT 1D receptors causes [Ca 2ϩ ] i elevation through the PTX-sensitive mechanism in other cells. 23,24 In this study, we have verified that activation of endogenous vascular 5-HT 1B/1D receptors by SUM and serotonin causes Ca 2ϩ mobilization and subsequent contraction through a PTX-sensitive pathway in vascular tissue preparations. Moreover, this is the first study demonstrating that activation of endogenous vascular 5-HT 1B receptors contribute to hypercontractions, concomitant with augmented Ca 2ϩ mobilization in atherosclerotic vessels.…”

Section: Discussionmentioning

confidence: 79%

Serotonin-Induced Hypercontraction Through 5-Hydroxytryptamine 1B Receptors in Atherosclerotic Rabbit Coronary Arteries

et al. 2001

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Background-Augmented vasoconstriction to serotonin (5-hydroxytryptamine ) in atherosclerotic vessels plays a crucial role in the development of myocardial ischemia. We investigated mechanisms for serotonin-evoked hypercontraction in atherosclerotic rabbit coronary arteries. Methods and Results-Contractile responses to serotonergic agents of endothelium-denuded coronary arteries from control and Watanabe heritable hyperlipidemic rabbits (WHHL) were examined. WHHL coronary arteries exhibited hypercontraction to 5-HT 1 -receptor agonists; the constrictor threshold concentrations and ED 50 to serotonin, 5-carboxamidotryptamine, and sumatriptan in WHHL were significantly lower, and the E max in WHHL to these agents were increased 55% to 59% above those of the control. Serotonin-evoked contractions in both groups were inhibited by GR127935 (5-HT 1B/1D antagonist; 0.1 to 1 nmol/L) and pertussis toxin but not by ketanserin (5-HT 2 antagonist; 0.01 to 1 mol/L), suggesting that the hypercontraction is most likely mediated by 5-HT 1B/1D receptors through a pertussis toxin-sensitive pathway. Furthermore, simultaneous measurements of [Ca 2ϩ ] i and isometric tension of fura-2-loaded arteries revealed that the hypercontraction was concomitant with the augmented elevation of [Ca 2ϩ ] i in the smooth muscle. The 5-HT 1B mRNA levels in WHHL coronary arteries increased to 2.5-fold over those in control arteries, whereas neither 5-HT 1D nor 5-HT 2A mRNA was detected in either group. Conclusions-Atherosclerotic rabbit coronary arteries exhibited the enhancement in contraction and Ca 2ϩ mobilization in response to serotonin. The 5-HT 1B receptor, which is upregulated by atherosclerosis, most likely mediates the augmenting effects of serotonin.

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Section: Discussionmentioning

confidence: 79%

Serotonin-Induced Hypercontraction Through 5-Hydroxytryptamine 1B Receptors in Atherosclerotic Rabbit Coronary Arteries

et al. 2001

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“…The Ca 2ϩ response induced by the native ligand 5-HT is likely to occur via activation of the recombinant 5-HT 1A receptor; no Ca 2ϩ signal could be detected in nontransfected CHO-K1 cells, although the Ca 2ϩ pathway was adequately responsive to bradykinin. CHO cells have previously been reported to express endogenous 5-HT 1B receptors, which are negatively coupled to adenylyl cyclase and positively coupled to increases in intracellular Ca 2ϩ formation (Dickenson and Hill, 1995;Giles et al, 1996). In the present study, the selective 5-HT 1B receptor antagonist SB 224289 (Gaster et al, 1998) affected the 5-HT-mediated Ca 2ϩ response little, if at all, whereas the selective 5-HT 1A receptor antagonist WAY 100635 (Fletcher et al, 1996) (Fargin et al, 1991), this may be different for CHO-K1 and C6-glial cells.…”

Section: Discussionmentioning

confidence: 99%

Ca²⁺Responses in Chinese Hamster Ovary-K1 Cells Demonstrate an Atypical Pattern of Ligand-Induced 5-HT_1AReceptor Activation

Pauwels¹,

Colpaert²

2003

J Pharmacol Exp Ther

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Little experimental evidence has been reported for diverse signaling via 5-hydroxytryptamine (5-HT) 1A receptors despite the fact that agonists seem to be more efficacious at dorsal raphe somatodendritic 5-HT 1A autoreceptors than at postsynaptic 5-HT 1A receptors. The present study investigated Ca 2ϩ responses in Chinese hamster ovary (CHO)-K1 cells expressing a human 5-HT 1A receptor by 5-HT, prototypical 5-HT

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“…Furthermore, 5-HT 7A coupling to adenylyl cyclases occurs independent of G i . Several other G protein-linked members of the 5-HT receptor family, including 5-HT 1A , 5-HT 1D , 5-HT 1F , 5-HT 2C , and 5-HT 4 couple to increases in calcium (54 -58), and endogenously expressed 5-HT 1B and 5-HT 2B receptors increase intracellular calcium independent of phosphoinositide turnover (59,60).…”

Section: -Ht 7a Increases Intracellular Ca 2ϩmentioning

confidence: 99%

Stimulation of Type 1 and Type 8 Ca2+/Calmodulin-sensitive Adenylyl Cyclases by the Gs-coupled 5-Hydroxytryptamine Subtype 5-HT7AReceptor

Baker

Nielsen

Impey

et al. 1998

Journal of Biological Chemistry

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The neurotransmitter serotonin (5-hydroxytryptamine, 5-HT) plays an important regulatory role in developing and adult nervous systems. With the exception of the 5-HT 3 receptor, all of the cloned serotonin receptors belong to the G protein-coupled receptor superfamily. Subtypes 5-HT 6 and 5-HT 7 couple to stimulation of adenylyl cyclases through G s and display high affinities for antipsychotic and antidepressant drugs. In the brain, mRNA for 5-HT 6 is found at high levels in the hippocampus, striatum, and nucleus accumbens. 5-HT 7 mRNA is most abundant in the hippocampus, neocortex, and hypothalamus. To better understand how serotonin might control cAMP levels in the brain, we coexpressed 5-HT 6 or 5-HT 7A receptors with specific isoforms of adenylyl cyclase in HEK 293 cells. The 5-HT 6 receptor functioned as a typical G s -coupled receptor in that it stimulated AC5, a G s -sensitive adenylyl cyclase, but not AC1 or AC8, calmodulin (CaM)-stimulated adenylyl cyclases that are not activated by G s -coupled receptors in vivo. Surprisingly, serotonin activation of 5-HT 7A stimulated AC1 and AC8 by increasing intracellular Ca 2؉ . 5-HT also increased intracellular Ca 2؉ in primary neuron cultures. These data define a novel mechanism for the regulation of intracellular cAMP by serotonin. Serotonin (5-hydroxytryptamine, 5-HT)1 is a ubiquitous neurotransmitter that elicits a variety of physiological effects peripherally and centrally (1-3). A growing family of plasma membrane receptors bind 5-HT and mediate its cellular effects (4). All of the 5-HT receptors except 5-HT 3 belong to the superfamily of G protein-coupled receptors. The recently cloned 5-HT 6 (5, 6) and 5-HT 7 (7-10) receptors activate adenylyl cyclase(s) through the heterotrimeric G protein G s , and expression of these receptors in cultured cells couples serotonin to increases in cAMP (6,8). 5-HT 6 and 5-HT 7 display high affinities for antipsychotic and antidepressant drugs including clozapine, amoxapine, and amitryptiline (5-8), suggesting a role for these receptors in affective function. In the brain, the 5-HT 6 receptor is most highly expressed in the hippocampus, nucleus accumbens, striatum, and limbic regions, and the 5-HT 7 receptor is found in the hypothalamus, hippocampus, and cortex. The distribution of these receptors in brain is consistent with the hypothesis that they play a role in mood and affect (8,(11)(12)(13). In addition, the expression of the 5-HT 7 receptor in the suprachiasmatic nucleus (SCN) and the ability of serotonin and cAMP to advance the mammalian circadian rhythm indicates that 5-HT 7 plays an important role in circadian physiology (10, 14, 15). 5-HT 7 receptors are also expressed in glial cells (16,17) and at lower levels in peripheral tissues including the spleen, intestine, and vascular smooth muscle (7-9, 18).Many psychotherapeutic agents modulate the cAMP signaling pathway (19) and perturbation of this signal transduction system may contribute to some affective disorders. To date, nine distinct cDNA clones for mammalian...

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Coupling of an endogenous 5‐HT_1B‐like receptor to increases in intracellular calcium through a pertussis toxin‐sensitive mechanism in CHO‐K1 cells

Cited by 24 publications

References 36 publications

Serotonin-Induced Hypercontraction Through 5-Hydroxytryptamine 1B Receptors in Atherosclerotic Rabbit Coronary Arteries

Serotonin-Induced Hypercontraction Through 5-Hydroxytryptamine 1B Receptors in Atherosclerotic Rabbit Coronary Arteries

Ca²⁺Responses in Chinese Hamster Ovary-K1 Cells Demonstrate an Atypical Pattern of Ligand-Induced 5-HT_1AReceptor Activation

Stimulation of Type 1 and Type 8 Ca2+/Calmodulin-sensitive Adenylyl Cyclases by the Gs-coupled 5-Hydroxytryptamine Subtype 5-HT7AReceptor

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Coupling of an endogenous 5‐HT1B‐like receptor to increases in intracellular calcium through a pertussis toxin‐sensitive mechanism in CHO‐K1 cells

Cited by 24 publications

References 36 publications

Serotonin-Induced Hypercontraction Through 5-Hydroxytryptamine 1B Receptors in Atherosclerotic Rabbit Coronary Arteries

Serotonin-Induced Hypercontraction Through 5-Hydroxytryptamine 1B Receptors in Atherosclerotic Rabbit Coronary Arteries

Ca2+Responses in Chinese Hamster Ovary-K1 Cells Demonstrate an Atypical Pattern of Ligand-Induced 5-HT1AReceptor Activation

Stimulation of Type 1 and Type 8 Ca2+/Calmodulin-sensitive Adenylyl Cyclases by the Gs-coupled 5-Hydroxytryptamine Subtype 5-HT7AReceptor

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Coupling of an endogenous 5‐HT_1B‐like receptor to increases in intracellular calcium through a pertussis toxin‐sensitive mechanism in CHO‐K1 cells

Ca²⁺Responses in Chinese Hamster Ovary-K1 Cells Demonstrate an Atypical Pattern of Ligand-Induced 5-HT_1AReceptor Activation