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- Publisher Website: 10.1016/S0304-4165(98)00079-8
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- PMID: 9813359
- WOS: WOS:000076324900028
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Article: Fluorescent analogs of NAADP with calcium mobilizing activity
Title | Fluorescent analogs of NAADP with calcium mobilizing activity |
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Authors | |
Keywords | ADP-ribosyl cyclase Ca2+ mobilization Ca2+ signaling Ca2+ store Cyclic ADP-ribose Nicotinic acid adenine dinucleotide phosphate, fluorescent analogs of |
Issue Date | 1998 |
Publisher | Elsevier BV. The Journal's web site is located at http://www.elsevier.com/locate/bbagen |
Citation | Biochimica Et Biophysica Acta - General Subjects, 1998, v. 1425 n. 1, p. 263-271 How to Cite? |
Abstract | Nicotinic acid adenine dinucleotide phosphate (NAADP) mobilizes Ca2+ through a mechanism totally independent of cyclic ADP-ribose or inositol trisphosphate. Fluorescent analogs of NAADP were synthesized in this study to facilitate further characterization of this novel Ca2+ release mechanism. The base-exchange reaction catalyzed by ADP-ribosyl cyclase was utilized to convert nicotinamide 1,N6-ethenoadenine dinucleotide phosphate to a fluorescent product, nicotinic acid 1,N6-ethenoadenine dinucleotide phosphate (etheno-NAADP). The excitation spectrum of the product showed two maxima at 275 nm and 300 nm and an emission maximum at 410 nm. An aza derivative of etheno-NAADP was also synthesized by sequential treatments with NaOH and nitrite. The product, nicotinic acid 1,N6-etheno-2-aza-adenine dinucleotide phosphate (etheno-aza-NAADP) had excitation maxima at 280 nm and 360 nm and an emission maximum at 470 nm. The fluorescence of both analogs was sensitive to polarity and exhibited a 3-4-fold enhancement going from an aqueous buffer to an organic solvent. Proton-NMR measurements confirmed the presence of the etheno ring in both analogs. In the aza derivative the proton at the 2-position of the adenine ring was absent, consistent with the conversion of the 2-carbon to a nitrogen. Both analogs could activate Ca2+ release from sea urchin egg homogenates and the half-maximal concentrations for etheno-aza-NAADP and etheno-NAADP were at about 2.5 μM and 5 μM, respectively. At sub-threshold concentrations, both analogs could also function as antagonists, inactivating the NAADP-sensitive Ca2+ release with a half-maximal concentration of 60-80 nM. Microinjection of etheno-aza-NAADP into live eggs activated Ca2+ increase and triggered a cortical exocytotic reaction confirming its effectiveness in vivo. These fluorescent analogs are potentially useful for visualizing the novel Ca2+ stores that are sensitive to NAADP in live cells. Copyright (C) 1998 Elsevier Science B.V. |
Persistent Identifier | http://hdl.handle.net/10722/171657 |
ISSN | 2023 Impact Factor: 2.8 2023 SCImago Journal Rankings: 0.767 |
ISI Accession Number ID | |
References |
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Lee, HC | en_US |
dc.contributor.author | Aarhus, R | en_US |
dc.date.accessioned | 2012-10-30T06:16:12Z | - |
dc.date.available | 2012-10-30T06:16:12Z | - |
dc.date.issued | 1998 | en_US |
dc.identifier.citation | Biochimica Et Biophysica Acta - General Subjects, 1998, v. 1425 n. 1, p. 263-271 | en_US |
dc.identifier.issn | 0304-4165 | en_US |
dc.identifier.uri | http://hdl.handle.net/10722/171657 | - |
dc.description.abstract | Nicotinic acid adenine dinucleotide phosphate (NAADP) mobilizes Ca2+ through a mechanism totally independent of cyclic ADP-ribose or inositol trisphosphate. Fluorescent analogs of NAADP were synthesized in this study to facilitate further characterization of this novel Ca2+ release mechanism. The base-exchange reaction catalyzed by ADP-ribosyl cyclase was utilized to convert nicotinamide 1,N6-ethenoadenine dinucleotide phosphate to a fluorescent product, nicotinic acid 1,N6-ethenoadenine dinucleotide phosphate (etheno-NAADP). The excitation spectrum of the product showed two maxima at 275 nm and 300 nm and an emission maximum at 410 nm. An aza derivative of etheno-NAADP was also synthesized by sequential treatments with NaOH and nitrite. The product, nicotinic acid 1,N6-etheno-2-aza-adenine dinucleotide phosphate (etheno-aza-NAADP) had excitation maxima at 280 nm and 360 nm and an emission maximum at 470 nm. The fluorescence of both analogs was sensitive to polarity and exhibited a 3-4-fold enhancement going from an aqueous buffer to an organic solvent. Proton-NMR measurements confirmed the presence of the etheno ring in both analogs. In the aza derivative the proton at the 2-position of the adenine ring was absent, consistent with the conversion of the 2-carbon to a nitrogen. Both analogs could activate Ca2+ release from sea urchin egg homogenates and the half-maximal concentrations for etheno-aza-NAADP and etheno-NAADP were at about 2.5 μM and 5 μM, respectively. At sub-threshold concentrations, both analogs could also function as antagonists, inactivating the NAADP-sensitive Ca2+ release with a half-maximal concentration of 60-80 nM. Microinjection of etheno-aza-NAADP into live eggs activated Ca2+ increase and triggered a cortical exocytotic reaction confirming its effectiveness in vivo. These fluorescent analogs are potentially useful for visualizing the novel Ca2+ stores that are sensitive to NAADP in live cells. Copyright (C) 1998 Elsevier Science B.V. | en_US |
dc.language | eng | en_US |
dc.publisher | Elsevier BV. The Journal's web site is located at http://www.elsevier.com/locate/bbagen | en_US |
dc.relation.ispartof | Biochimica et Biophysica Acta - General Subjects | en_US |
dc.subject | ADP-ribosyl cyclase | - |
dc.subject | Ca2+ mobilization | - |
dc.subject | Ca2+ signaling | - |
dc.subject | Ca2+ store | - |
dc.subject | Cyclic ADP-ribose | - |
dc.subject | Nicotinic acid adenine dinucleotide phosphate, fluorescent analogs of | - |
dc.subject.mesh | Adp-Ribosyl Cyclase | en_US |
dc.subject.mesh | Animals | en_US |
dc.subject.mesh | Antigens, Cd | en_US |
dc.subject.mesh | Antigens, Cd38 | en_US |
dc.subject.mesh | Antigens, Differentiation - Metabolism | en_US |
dc.subject.mesh | Calcium - Metabolism | en_US |
dc.subject.mesh | Female | en_US |
dc.subject.mesh | Fluorescent Dyes - Chemistry | en_US |
dc.subject.mesh | Ion Transport - Drug Effects | en_US |
dc.subject.mesh | Magnetic Resonance Spectroscopy | en_US |
dc.subject.mesh | Nad+ Nucleosidase - Metabolism | en_US |
dc.subject.mesh | Nadp - Analogs & Derivatives - Chemistry - Pharmacology | en_US |
dc.subject.mesh | Ovum - Drug Effects - Metabolism | en_US |
dc.subject.mesh | Sea Urchins | en_US |
dc.subject.mesh | Spectrometry, Fluorescence | en_US |
dc.title | Fluorescent analogs of NAADP with calcium mobilizing activity | en_US |
dc.type | Article | en_US |
dc.identifier.email | Lee, HC:leehc@hku.hk | en_US |
dc.identifier.authority | Lee, HC=rp00545 | en_US |
dc.description.nature | link_to_subscribed_fulltext | en_US |
dc.identifier.doi | 10.1016/S0304-4165(98)00079-8 | en_US |
dc.identifier.pmid | 9813359 | - |
dc.identifier.scopus | eid_2-s2.0-0032538101 | en_US |
dc.relation.references | http://www.scopus.com/mlt/select.url?eid=2-s2.0-0032538101&selection=ref&src=s&origin=recordpage | en_US |
dc.identifier.volume | 1425 | en_US |
dc.identifier.issue | 1 | en_US |
dc.identifier.spage | 263 | en_US |
dc.identifier.epage | 271 | en_US |
dc.identifier.isi | WOS:000076324900028 | - |
dc.publisher.place | Netherlands | en_US |
dc.identifier.scopusauthorid | Lee, HC=26642959100 | en_US |
dc.identifier.scopusauthorid | Aarhus, R=6701339421 | en_US |
dc.identifier.issnl | 0304-4165 | - |