PXD066711

PXD066711 is an original dataset announced via ProteomeXchange.

Title	The identification of adenylyl cyclase modulators as potential receptors for 6-nitrodopamine in human-induced pluripotent stem cell (hiPSC)-derived cardiomyocytes and their relevance in heart inotropism
Description	6-Nitrodopamine Q7 Q8 (6-ND Q9 ) has potent positive chronotropic and inotropic effects. At a very low dose, i.e., 10 fM, it causes potentiation of the positive chronotropic effects induced by catecholamines in the rat atria, indicating a distinct mechanism of action. Cyclase-associated proteins (CAP-1 and CAP-2) are potential receptors for 6-ND in human cardiomyocytes. Since cyclic 3′,5′-cyclic adenosine monophosphate (cAMP) plays a fundamental role in the positive inotropic effects of classical catecholamines, it was further investigated whether 6-ND potentiates the positive inotropic effects induced by classical catecholamines in the rat isolated perfused heart. Human-induced pluripotent stem cell (hiPSC)- derived cardiomyocytes were harvested and lysed, and following appropriate separation procedures, membrane proteins were incubated with 6-NDderivatized agarose, centrifuged, and the proteins retained in the agarose eluted with 6-ND (1 mM). The proteins isolated from the chemical pulldown assay were fractionated by SDS-PAGE, the bands were cut and hydrolyzed in situ with trypsin, and then separated and sequenced. A total of 817 proteins were generated, and following screening using UniProt “Retrieve/ID Mapping” function and Gene Ontology cellular component category, 124 proteins were identified as membrane proteins. These experiments identified three proteins that modulate adenylyl cyclase (AC) activity (CAP-1, CAP-2, and STIM1), which are compatible with the pharmacological findings reported for 6-ND in the rat heart. As expected, 6-ND strongly potentiates the inotropic effect induced by noradrenaline in Langendorff’s preparation. In conclusion, 6-ND-induced potentiation of catecholamine-induced chronotropic and inotropic effects is due to the modulation of adenylyl cyclase activity, probably via direct interactions with CAP-1 and CAP-2.
HostingRepository	PRIDE
AnnounceDate	2025-09-08
AnnouncementXML	Submission_2025-09-07_16:41:00.894.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Flora Cozzolino
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	iodoacetamide derivatized residue
Instrument	LTQ Orbitrap

Revision	Datetime	Status	ChangeLog Entry
0	2025-07-29 03:56:12	ID requested
⏵ 1	2025-09-07 16:41:01	announced

10.3389/fphar.2025.1597035;

Cipollone I, Monaco V, Britto-J, ú, nior J, Lima AT, Antunes E, Pupo AS, Iacobucci I, Cozzolino F, Monti M, Parisi S, Divisato G, Cascone E, De Simone A, Corvino A, Fiorino F, Frecentese F, Santagada V, Severino B, Sparaco R, Cinque P, Vertuccio S, Caliendo G, De Nucci G, The identification of adenylyl cyclase modulators as potential receptors for 6-nitrodopamine in human-induced pluripotent stem cell (hiPSC)-derived cardiomyocytes and their relevance in heart inotropism. Front Pharmacol, 16():1597035(2025) [pubmed]

submitter keyword: adrenaline, stromal interaction molecule 1, cyclase- Q10 associated proteins,dopamine, nitro-catecholamine

Maria Monti
contact affiliation	University of Naples Federico II
contact email	montimar@unina.it
lab head
Flora Cozzolino
contact affiliation	University of Naples "Federico II"
contact email	flora.cozzolino@unina.it
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD066711
     1. Label: PRIDE project
     2. Name: The identification of adenylyl cyclase modulators as potential receptors for 6-nitrodopamine in human-induced pluripotent stem cell (hiPSC)-derived cardiomyocytes and their relevance in heart inotropism