Human platelets possess multiple [3H]imipramine binding sites.

J R Ieni; S R Zukin; H M Van Praag

doi:10.1016/0014-2999(84)90078-5

Home/Archive/PubMed

PubMed · 6097465

Human platelets possess multiple [3H]imipramine binding sites.

J R Ieni·S R Zukin·H M Van Praag

View original source ↗Export metadata ↓

Abstract

Scatchard analysis of [3H]imipramine binding to human platelets over the concentration range of 0.1-250 nM revealed a biphasic concave upward curve. Computer-assisted analysis indicated the best fit of the data by a two-site model with apparent Kd values of 0.68 and 293 nM and apparent Bmax values of 802 fmol/mg protein and 12.72 pmol/mg protein for the high- and low-affinity components, respectively. These results demonstrate the complex manner in which [3H]imipramine binding to human platelets, suggesting a reason for inconsistencies in Bmax values reported in the literature. Further studies of these low- as well as high-affinity sites may help elucidate the functional role of [3H]imipramine binding sites in affective disorders.

Explore related subjects

Blood Platelets Carrier Proteins Humans Imipramine In Vitro Techniques Kinetics Receptors, Drug Receptors, Neurotransmitter Tritium Journal Article Research Support, U.S. Gov't, P.H.S.

Keep this discovery

Explore connections, maps & timelines

BibTeX RIS

J R Ieni, S R Zukin, H M Van Praag. 1984-11-27. Human platelets possess multiple [3H]imipramine binding sites.. https://doi.org/10.1016/0014-2999(84)90078-5

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

PubMed2026

Dynamic lysine acetylation and succinylation of platelet proteins regulates platelet storage lesion: mechanistic insights from multi-omics.

OBJECTIVES: Platelet storage lesion (PSL) severely impairs platelet function during storage, presenting a major hurdle in transfusion medicine; however, the dynamic interplay between global proteomic changes and post-translational modifications (PTMs) underlying these functional deteriorations remains insufficiently characterized. Here, we report the first comprehensive multi-omics analysis integrating global proteomics, acetylomics, and succinylomics to dissect the molecular dynamics during platelet storage. METHODS: We performed quantification of global proteomics, acetylome and succinylome based on TMT-labeled LC-MS/MS analysis, combined with antibody-affinity enrichment and purification. Dynamic molecular changes and functional transformation of platelet were also characterized under proper conditions stored for 1, 3, 5, 7 days, respectively. RESULTS: We systematically characterized 3,609 proteins, 1,308 acetylation sites, and 1,947 succinylation sites across multiple storage time points (D1, D3, D5, D7). We distinct temporal patterns of post-translational modifications, with succinylation showing more extensive coverage than acetylation in platelets. Pathway enrichment analysis revealed extensive metabolic reprogramming involving complement activation, energy metabolism, and cellular detoxification processes. The identification of specific motif patterns provided mechanistic insights into the functional specificity of these modifications. Random forest machine learning identified 20 core regulatory proteins representing critical nodes in PSL development. Furthermore, we employed real - time quantitative polymerase chain reaction (RT - QPCR) to measure the expression levels of key genes related to platelet function and PTM - associated pathways. CONCLUSION: By mapping the interplay between proteomic abundance shifts and PTM dynamics, this study provides a multidimensional understanding of PSL, establishing a foundational framework for optimizing storage protocols and enhancing transfusion safety.

Blood Platelets↗

PubMed2007

Saxatilin, a snake venom disintegrin, regulates platelet activation associated with human vascular endothelial cell migration and invasion.

BACKGROUND: Platelet activation results in platelet aggregation and the secretion of granules, which contain a variety of constituents including nonprotein molecules, adhesive proteins and hydrolases. The platelet-derived supernatant (PDS), which contains these granules, is known to trigger the activation of endothelium and chemotaxis of monocytes. METHODS AND RESULTS: PDS derived from collagen-activated platelets stimulated human umbilical vein endothelial cell (HUVEC) migration and invasion, as measured through the use of a Boyden chamber. This collagen-induced PDS also triggered integrin alpha(v)beta(3) upregulation in HUVECs. The inclusion of a neutralizing antibody to platelet-derived growth factor (PDGF)-B abolished HUVEC migration/invasion and integrin alpha(v)beta(3) upregulation, showing that PDGF-AB mediates the proangiogenic effects of collagen-activated PDS. Saxatilin, a snake venom disintegrin known to interrupt platelet aggregation by antagonizing integrin alpha(IIb)beta(3), inhibited the collagen-induced platelet activation and abolished the angiogenic properties of PDS. Saxatilin also inhibited the collagen-induced phosphorylation of Syk, a key mediator of inside-out signaling in platelet activation. CONCLUSION: Saxatilin inhibits platelet activation, platelet PDGF-AB release as well as subsequent endothelial cell migration and invasion.

Blood Platelets↗

PubMed2007

Nongenomic signaling of the retinoid X receptor through binding and inhibiting Gq in human platelets.

Retinoid X receptors (RXRs) are important transcriptional nuclear hormone receptors, acting as either homodimers or the binding partner for at least one fourth of all the known human nuclear receptors. Functional nongenomic effects of nuclear receptors are poorly understood; however, recently peroxisome proliferator-activated receptor (PPAR) gamma, PPARbeta, and the glucocorticoid receptor have all been found active in human platelets. Human platelets express RXRalpha and RXRbeta. RXR ligands inhibit platelet aggregation and TXA(2) release to ADP and the TXA(2) receptors, but only weakly to collagen. ADP and TXA(2) both signal via the G protein, Gq. RXR rapidly binds Gq but not Gi/z/o/t/gust in a ligand-dependent manner and inhibits Gq-induced Rac activation and intracellular calcium release. We propose that RXR ligands may have beneficial clinical actions through inhibition of platelet activation. Furthermore, our results demonstrate a novel nongenomic mode for nuclear receptor action and a functional cross-talk between G-protein and nuclear receptor signaling families.

Blood Platelets↗