α1b-Adrenoceptor-Mediated Calcium Oscillation is Specific for the S Phase in Cell Cycle and Dependent on the Extracellular Calcium

doi:10.1006/bbrc.1996.0987

Biochemical and Biophysical Research Communications

Volume 224, Issue 1, 5 July 1996, Pages 80-86

https://doi.org/10.1006/bbrc.1996.0987 Get rights and content

Abstract

Using Chinese hamster ovary cells stably expressing α_1b-adrenoceptor (α_1bAR) as a model, we examined the effect of the cell cycle on the agonist-promoted intracellular [Ca²⁺]_ioscillation. In cells synchronized into either the G₁state or the M phase, no oscillatory behavior was observed under any extracellular Ca²⁺concentrations ([Ca²⁺]_o≤ 3 mM), whereas in cells synchronized into the S phase, norepinephrine caused [Ca²⁺]_ioscillation in a [Ca²⁺]_o-dependent manner, indicating that α₁AR-mediated [Ca²⁺]_ioscillation is specific for the S phase in cell cycle and dependent on [Ca²⁺]_o. The S phase-specific occurrence of α₁AR-mediated [Ca²⁺]_ioscillation is not associated with changes in α₁AR density. As the cells consistently developed [Ca²⁺]_ioscillation in the S phase, the cells would provide a valuable system to study further the biochemical mechanism for agonist-induced [Ca²⁺]_ioscillation phenomenon.

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Cited by (5)

Pharmacological lineage analysis revealed the binding affinity of broad-spectrum substance P antagonists to receptors for gonadotropin-releasing peptide
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Citation Excerpt :
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A group of synthetic substance P (SP) antagonists, such as [Arg⁶,D-Trp^7,9,N^MePhe⁸]-substance P(6-11) and [D-Arg¹,D-Phe⁵,D-Trp^7,9,Leu¹¹]-substance P, bind to a range of distinct G-protein-coupled receptor (GPCR) family members, including V_1a vasopressin receptors, and they competitively inhibit agonist binding. This extended accessibility enabled us to identify a GPCR subset with a partially conserved binding site structure. By combining pharmacological data and amino acid sequence homology matrices, a pharmacological lineage of GPCRs that are sensitive to these two SP antagonists was constructed. We found that sensitivity to the SP antagonists was not limited to the Gq-protein-coupled V_1a and V_1b receptors; Gs-coupled V₂ receptors and oxytocin receptors, which couple with both Gq and Gi, also demonstrated sensitivity. Unexpectedly, a dendrogram based on the amino acid sequences of 222 known GPCRs showed that a group of receptors sensitive to the SP antagonists are located in close proximity to vasopressin/oxytocin receptors. Gonadotropin-releasing peptide receptors, located near the vasopressin receptors in the dendrogram, were also sensitive to the SP analogs, whereas α_1B adrenergic receptors, located more distantly from the vasopressin receptors, were not sensitive. Our finding suggests that pharmacological lineage analysis is useful in selecting subsets of candidate receptors that contain a conserved binding site for a ligand with broad-spectrum binding abilities. The knowledge that the binding site of the two broad-spectrum SP analogs partially overlaps with that of distinct peptide agonists is valuable for understanding the specificity/broadness of peptide ligands.
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¹: Present address: Department of OB/GYN, NKK Hospital, Kawasaki, 210 Japan.

²: To whom correspondence should be addressed. Fax: Japan-3-3419-1252. E-mail: [email protected].

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Biochemical and Biophysical Research Communications

Regular Articleα1b-Adrenoceptor-Mediated Calcium Oscillation is Specific for the S Phase in Cell Cycle and Dependent on the Extracellular Calcium

Abstract

Pharmacological lineage analysis revealed the binding affinity of broad-spectrum substance P antagonists to receptors for gonadotropin-releasing peptide

Differences in the subcellular localization of α<inf>1</inf>-adrenoceptor subtypes can affect the subtype selectivity of drugs in a study with the fluorescent ligand BODIPY FL-prazosin

α<inf>1</inf>-Adrenergic receptor activation of c-fos expression in transfected rat-1 fibroblasts: Role of Ca<sup>2+</sup><sup>1</sup>

Differential mechanism for the cell surface sorting and agonist-promoted internalization of the α(1B)-adrenoceptor

Subtype-specific differences in subcellular localization of α<inf>1</inf>- adrenoceptors: Chlorethylclonidine preferentially alkylates the accessible cell surface α<inf>1</inf>-adrenoceptors irrespective of the subtype

Regular Article
α_1b-Adrenoceptor-Mediated Calcium Oscillation is Specific for the S Phase in Cell Cycle and Dependent on the Extracellular Calcium