# Topics and Trends in Most Cited Receptor Mechanisms and Signaling Papers, Class of 2026

*Canonical URL: https://pri.pepkio.com/top-papers/receptor-mechanisms-and-signaling/2026*

## What topics and trends defined most-cited Receptor Mechanisms and Signaling research in the Class of 2026?

The Class of 2026 highlights a 5-fold surge in μ-opioid receptor research and the rapid rise of positive allosteric modulators and optogenetic stimulation. High-resolution cryo-EM and GLP-1 receptor signaling remain central, while studies on biased agonism declined sharply, shifting emphasis toward circuit-level neuromodulation and metabolic receptor targeting.

## At a glance

| Fact | Value |
| --- | --- |
| Field | Receptor Mechanisms and Signaling |
| Cohort label | Class of 2026 (2024 publications) |
| Papers analyzed | 3,950 |
| Papers ranked | 20 |
| Top topics in ranked papers | μ-opioid receptor, GLP-1 receptor, cryo-electron microscopy, β-arrestin recruitment |
| Publication window | Jan 1, 2024 – Dec 31, 2024 |
| Eligibility | Research articles; reviews excluded |
| Citation window | 18 months post-publication |
| 18m citation range | 41–116 |
| Data source | OpenAlex · Retrieved July 2026 |
| License | CC BY 4.0 |

## Rankings

| Rank | Title | Authors | Corresponding authors | Affiliation | Journal | 18m citations | DOI |
| ---: | --- | --- | --- | --- | --- | ---: | --- |
| 1 | A GIPR antagonist conjugated to GLP-1 analogues promotes weight loss with improved metabolic parameters in preclinical and phase 1 settings | Murielle M Véniant, Shu-Chen Lu, Larissa Atangan, Renee Komorowski, Shanaka Stanislaus, Yuan Cheng, Bin Wu, James R Falsey, Todd Hager, Veena A Thomas, Malhar Ambhaikar, Lucie Sharpsten, Yineng Zhu, Vamsi Kurra, Rohini Jeswani, Rajneet K Oberoi, Jane R Parnes, Narimon Honarpour, Joel Neutel, Jennifer L Strande | Murielle M. Véniant | Amgen Research, United States | Nature Metabolism | 116 | 10.1038/s42255-023-00966-w |
| 2 | Dissociable hindbrain GLP1R circuits for satiety and aversion | Kuei-Pin Huang, Alisha A Acosta, Misgana Y Ghidewon, Aaron D McKnight, Milena S Almeida, Nathaniel T Nyema, Nicholas D Hanchak, Nisha Patel, Yenoukoume S K Gbenou, Alice E Adriaenssens, Kevin A Bolding, Amber L Alhadeff | Amber L. Alhadeff | Monell Chemical Senses Center, United States | Nature | 109 | 10.1038/s41586-024-07685-6 |
| 3 | Efficacy and Safety of Xanomeline-Trospium Chloride in Schizophrenia | Inder Kaul, Sharon Sawchak, David P Walling, Carol A Tamminga, Alan Breier, Haiyuan Zhu, Andrew C Miller, Steven M Paul, Stephen K Brannan | Steven M. Paul | Karuna Therapeutics, United States | JAMA Psychiatry | 99 | 10.1001/jamapsychiatry.2024.0785 |
| 4 | Homodimerization of CB2 cannabinoid receptor triggered by a bivalent ligand enhances cellular signaling | Gemma Navarro, Marc Gómez-Autet, Paula Morales, Joan Biel Rebassa, Claudia Llinas Del Torrent, Nadine Jagerovic, Leonardo Pardo, Rafael Franco | Nadine Jagerovic, Leonardo Pardo, Rafael Franco | Universitat de Barcelona, Spain | Pharmacological Research | 84 | 10.1016/j.phrs.2024.107363 |
| 5 | A concerted neuron–astrocyte program declines in ageing and schizophrenia | Emi Ling, James Nemesh, Melissa Goldman, Nolan Kamitaki, Nora Reed, Robert E Handsaker, Giulio Genovese, Jonathan S Vogelgsang, Sherif Gerges, Seva Kashin, Sulagna Ghosh, John M Esposito, Kiely Morris, Daniel Meyer, Alyssa Lutservitz, Christopher D Mullally, Alec Wysoker, Liv Spina, Anna Neumann, Marina Hogan, Kiku Ichihara, Sabina Berretta, Steven A McCarroll | Emi Ling, Sabina Berretta, Steven A. McCarroll | Broad Institute of MIT and Harvard, United States | Nature | 83 | 10.1038/s41586-024-07109-5 |
| 6 | AlphaFold3 versus experimental structures: assessment of the accuracy in ligand-bound G protein-coupled receptors | Xin-Heng He, Jun-Rui Li, Shi-Yi Shen, H Eric Xu | H. Eric Xu | Shanghai Institute of Materia Medica, China | Acta Pharmacologica Sinica | 77 | 10.1038/s41401-024-01429-y |
| 7 | Time-resolved cryo-EM of G-protein activation by a GPCR | Makaía M Papasergi-Scott, Guillermo Pérez-Hernández, Hossein Batebi, Yang Gao, Gözde Eskici, Alpay B Seven, Ouliana Panova, Daniel Hilger, Marina Casiraghi, Feng He, Luis Maul, Peter Gmeiner, Brian K Kobilka, Peter W Hildebrand, Georgios Skiniotis | Georgios Skiniotis | Stanford University, United States | Nature | 72 | 10.1038/s41586-024-07153-1 |
| 8 | GPCRdb in 2025: adding odorant receptors, data mapper, structure similarity search and models of physiological ligand complexes | Luis P Taracena Herrera, Søren N Andreassen, Jimmy Caroli, Ismael Rodríguez-Espigares, Ali A Kermani, György M Keserű, Albert J Kooistra, Gáspár Pándy-Szekeres, David E Gloriam | Luis P Taracena Herrera | University of Copenhagen, Denmark | Nucleic Acids Research | 65 | 10.1093/nar/gkae1065 |
| 9 | Dopamine reuptake and inhibitory mechanisms in human dopamine transporter | Yue Li, Xianping Wang, Yufei Meng, Tuo Hu, Jun Zhao, Renjie Li, Qinru Bai, Pu Yuan, Jun Han, Kun Hao, Yiqing Wei, Yunlong Qiu, Na Li, Yan Zhao | Yan Zhao | Chinese Academy of Sciences, China | Nature | 64 | 10.1038/s41586-024-07796-0 |
| 10 | Dopamine transients follow a striatal gradient of reward time horizons | Ali Mohebi, Wei Wei, Lilian Pelattini, Kyoungjun Kim, Joshua D Berke | Joshua D. Berke | University of California San Francisco, United States | Nature Neuroscience | 56 | 10.1038/s41593-023-01566-3 |
| 11 | Improved green and red GRAB sensors for monitoring spatiotemporal serotonin release in vivo | Fei Deng, Jinxia Wan, Guochuan Li, Hui Dong, Xiju Xia, Yipan Wang, Xuelin Li, Chaowei Zhuang, Yu Zheng, Laixin Liu, Yuqi Yan, Jiesi Feng, Yulin Zhao, Hao Xie, Yulong Li | Yulong Li | Peking University, China | Nature Methods | 55 | 10.1038/s41592-024-02188-8 |
| 12 | Periodic ER-plasma membrane junctions support long-range Ca2+ signal integration in dendrites | Lorena Benedetti, Ruolin Fan, Aubrey V Weigel, Andrew S Moore, Patrick R Houlihan, Mark Kittisopikul, Grace Park, Alyson Petruncio, Philip M Hubbard, Song Pang, C Shan Xu, Harald F Hess, Stephan Saalfeld, Vidhya Rangaraju, David E Clapham, Pietro De Camilli, Timothy A Ryan, Jennifer Lippincott-Schwartz | Lorena Benedetti | HHMI Janelia Research Campus, United States | Cell | 48 | 10.1016/j.cell.2024.11.029 |
| 13 | Monitoring norepinephrine release in vivo using next-generation GRABNE sensors | Jiesi Feng, Hui Dong, Julieta E Lischinsky, Jingheng Zhou, Fei Deng, Chaowei Zhuang, Xiaolei Miao, Huan Wang, Guochuan Li, Ruyi Cai, Hao Xie, Guohong Cui, Dayu Lin, Yulong Li | Jiesi Feng, Yulong Li | Peking University, China | Neuron | 47 | 10.1016/j.neuron.2024.03.001 |
| 14 | Distinct µ-opioid ensembles trigger positive and negative fentanyl reinforcement | Fabrice Chaudun, Laurena Python, Yu Liu, Agnes Hiver, Jennifer Cand, Brigitte L Kieffer, Emmanuel Valjent, Christian Lüscher | Christian Lüscher | University of Geneva, Switzerland | Nature | 47 | 10.1038/s41586-024-07440-x |
| 15 | RAS-ON inhibition overcomes clinical resistance to KRAS G12C-OFF covalent blockade | Marie-Julie Nokin, Alessia Mira, Enrico Patrucco, Biagio Ricciuti, Sophie Cousin, Isabelle Soubeyran, Sonia San José, Serena Peirone, Livia Caizzi, Sandra Vietti Michelina, Aurelien Bourdon, Xinan Wang, Daniel Alvarez-Villanueva, María Martínez-Iniesta, August Vidal, Telmo Rodrigues, Carmen García-Macías, Mark M Awad, Ernest Nadal, Alberto Villanueva, Antoine Italiano, Matteo Cereda, David Santamaría, Chiara Ambrogio | Antoîne Italiano, Matteo Cereda, David Santamarı́a, Chiara Ambrogio | University of Bordeaux, France | Nature Communications | 45 | 10.1038/s41467-024-51828-2 |
| 16 | Transport and inhibition mechanisms of the human noradrenaline transporter | Tuo Hu, Zhuoya Yu, Jun Zhao, Yufei Meng, Kristine Salomon, Qinru Bai, Yiqing Wei, Jinghui Zhang, Shujing Xu, Qiuyun Dai, Rilei Yu, Bei Yang, Claus J. Løland, Yan Zhao | Claus J. Løland, Yan Zhao | University of Chinese Academy of Sciences, China | Nature | 45 | 10.1038/s41586-024-07638-z |
| 17 | Molecular connectomics reveals a glucagon-like peptide 1-sensitive neural circuit for satiety | Addison N Webster, Jordan J Becker, Chia Li, Dana C Schwalbe, Damien Kerspern, Eva O Karolczak, Catherine B Bundon, Roberta A Onoharigho, Maisie Crook, Maira Jalil, Elizabeth N Godschall, Emily G Dame, Adam Dawer, Dylan Matthew Belmont-Rausch, Tune H Pers, Andrew Lutas, Naomi Habib, Ali D Güler, Michael J Krashes, John N Campbell | Michael J. Krashes, John N. Campbell | University of Virginia, United States | Nature Metabolism | 45 | 10.1038/s42255-024-01168-8 |
| 18 | Synthetic GPCRs for programmable sensing and control of cell behaviour | Nicholas A Kalogriopoulos, Reika Tei, Yuqi Yan, Peter M Klein, Matthew Ravalin, Bo Cai, Ivan Soltesz, Yulong Li, Alice Y Ting | Alice Y. Ting | Stanford University, United States | Nature | 44 | 10.1038/s41586-024-08282-3 |
| 19 | Ligand efficacy modulates conformational dynamics of the µ-opioid receptor | Jiawei Zhao, Matthias Elgeti, Evan S. O’Brien, Cecı́lia P. Sár, Amal EI Daibani, Jie Heng, Xiaoou Sun, Elizabeth White, Tao Che, Wayne L. Hubbell, Brian K. Kobilka, Chunlai Chen | Matthias Elgeti, Brian K. Kobilka, Chunlai Chen | Tsinghua University, China | Nature | 41 | 10.1038/s41586-024-07295-2 |
| 20 | A bitter anti-inflammatory drug binds at two distinct sites of a human bitter taste GPCR | Lior Peri, Donna Matzov, Dominic R Huxley, Alon Rainish, Fabrizio Fierro, Liel Sapir, Tara Pfeiffer, Lukas Waterloo, Harald Hübner, Yoav Peleg, Peter Gmeiner, Peter J McCormick, Dorothee Weikert, Masha Y Niv, Moran Shalev-Benami | Dorothée Weikert, Masha Y. Niv, Moran Shalev-Benami | The Hebrew University of Jerusalem, Israel | Nature Communications | 41 | 10.1038/s41467-024-54157-6 |

## Topic trends

### What Topics Define the Class of 2026?

The Class of 2026 in Receptor Mechanisms and Signaling is anchored by high-resolution structural and physiological characterizations of key G protein-coupled receptors (GPCRs). Research surrounding the μ-opioid receptor stands at the forefront, driven by novel therapeutic efforts targeting pain management and opioid addiction, with related compounds like fentanyl and naloxone gaining notable focus. Concurrently, metabolic GPCR signaling—particularly the GLP-1 receptor and glucagon-like peptide 1 pathways—remains a major focal point due to ongoing clinical interest in metabolic disease and obesity therapeutics. Structural determination tools, led by cryo-electron microscopy (cryo-EM) and computational structure prediction using AlphaFold, continue to serve as indispensible foundational methodologies across top-cited literature. Downstream signaling mechanisms are prominently featured through β-arrestin recruitment studies and genetically encoded fluorescent sensors for tracking neurochemical dynamics in vivo. Furthermore, neuropharmacology topics intersecting with striatal microcircuits—including the nucleus accumbens, dopamine transients, and schizophrenia therapeutics such as xanomeline-trospium chloride—demonstrate a strong integration between molecular receptor pharmacology and systems-level neural circuit function.

*Leading research themes*

### How Did Topics Shift from the Class of 2025 to the Class of 2026?

Comparing the Class of 2025 and Class of 2026 reveals significant thematic evolutions in receptor signaling and pharmacology. The most prominent upward trend is seen in μ-opioid receptor studies, which experienced a 5-fold increase in representation (from 2% to 10% normalized frequency). Novel pharmacological approaches gained dramatic traction, marked by the emergence of positive allosteric modulators (PAMs), negative allosteric modulators (NAMs), and orthosteric site targeting, all rising from near-zero baseline frequencies in 2025. In addition, experimental methodologies saw a surge in optogenetic stimulation, single-nucleus RNA sequencing, and transcriptomic profiling to decipher cell-type-specific receptor signaling. Conversely, research explicitly centered on biased agonism underwent a sharp decline, dropping by two-thirds from 12% in 2025 to 4% in 2026. While foundational structural tools like cryo-EM and AlphaFold maintained steady representation, the focus of top-ranked publications moved away from generalized ligand-binding kinetics toward specific circuit-level mechanisms, such as feeding behavior, reward prediction, and appetite regulation. This trajectory reflects a broader paradigm shift from abstract signaling bias toward targeted allosteric modulation and neurocircuit validation.

*How topics shifted year over year*

## Cite this ranking

```
Pepkio Research Index (PRI). Topics and Trends in Most Cited Receptor Mechanisms and Signaling Papers, Class of 2026. https://pri.pepkio.com/top-papers/receptor-mechanisms-and-signaling/2026. Accessed 2026-07-29.

Zheng Su, Tinsley Li, Thematic Shifts in Early-High-Impact Cancer Genomics and Diagnostics Research: A Bibliometric and Semantic Analysis. bioRxiv 2026.07.04.736459; doi: https://doi.org/10.64898/2026.07.04.736459
```