RPEP-00091 · 1988Radioactive beta-endorphin injected intravenously accumulated specifically in the lung and liver but not other tissues. Four lines of evidence confirmed this was specific receptor binding, not passive trapping.
First, adding excess unlabeled beta-endorphin reduced the labeled peptide in lung and liver.
Second, injecting unlabeled beta-endorphin via the femoral vein (which passes through the lungs first) rapidly increased blood levels of the pre-injected labeled peptide, displacing it from lung binding sites. Injection via the carotid artery (bypassing the lungs) did not have this effect.
Third, immunoreactive labeled peptide that had lost its receptor-binding ability did not accumulate in lung or liver.
Fourth, dynorphin (1-13) and ethylketocyclazocine (kappa agonist) displaced beta-endorphin from these sites, but DADLE (delta agonist) and naloxone (mu antagonist) did not. This pharmacological profile indicates kappa-type binding sites.
Sato, H; Sugiyama, Y; Sawada, Y; Iga, T; Hanano, M · Animal Study
RPEP-00160 · 1990Opioid peptides selectively inhibit non-cholinergic excitatory neurotransmission in airways via prejunctional receptors, with dynorphin being the most potent endogenous peptide.
Kamikawa, Y; Shimo, Y · In Vitro
RPEP-00275 · 1993Proenkephalin and prodynorphin mRNA found in NTS and other medullary nuclei. Unilateral vagotomy increased opioid mRNA in ipsilateral NTS.
Rutherfurd, S D; Gundlach, A L · Animal Study
RPEP-00350 · 1995Opioid peptide levels in respiratory brainstem regions change significantly between young and older piglets, and prenatal cocaine exposure disrupts this developmental pattern.
Zhang, C; Moss, I R · Animal Study
RPEP-00409 · 1997BPC-157 protected against lesions from both NO agonists and NO antagonists, suggesting a modulatory rather than one-directional effect on nitric oxide signaling.
Grabarevic, Z; Tisljar, M; Artukovic, B; Bratulic, M; Dzaja, P; Seiwerth, S; Sikiric, P; Peric, J; Geres, D; Kos, J · Animal Study
RPEP-00663 · 2001Elevated plasma beta-endorphin and met-enkephalin in COPD patients with acute respiratory failure inversely correlated with blood pressure, demonstrating endogenous opioid-mediated attenuation of the hypertensive stress response.
Fontana, F; Bernardi, P; Tartuferi, L; Boschi, S; Di Toro, R; Spampinato, S · Cross Sectional
RPEP-00700 · 2001BPC-157 attenuated both intratracheal HCl-induced lung lesions and associated gastric damage in rats, demonstrating cytoprotective effects extending beyond the GI tract to the respiratory system.
Stancic-Rokotov, D; Slobodnjak, Z; Aralica, J; Aralica, G; Perovic, D; Staresinic, M; Gjurasin, M; Anic, T; Zoricic, I; Buljat, G; Prkacin, I; Sikiric, P; Seiwerth, S; Rucman, R; Petek, M; Turkovic, B; Kokic, N; Jagic, V; Boban-Blagaic, A · Animal Study
RPEP-00871 · 2003Peripheral opioid receptor activation in airway mucosa increased net water absorption, affecting mucociliary transport — identifying an opioidergic regulation of tracheobronchial respiratory defense mechanisms.
Wang, Lian; Tiniakov, Ruslan L; Yeates, Donovan B · Animal Study
RPEP-01002 · 2004Natriuretic peptides (BNP, NT-proBNP) are clinically useful for distinguishing cardiac from respiratory causes of dyspnea, diagnosing pulmonary hypertension, and monitoring right ventricular function in patients with chronic respiratory disease.
Yap, Lok Bin; Mukerjee, Dev; Timms, Peter M; Ashrafian, Houman; Coghlan, John Gerard · Review
RPEP-01141 · 2006Plasma apelin levels differentiated between cardiac and pulmonary disease causes and provided complementary prognostic information alongside natriuretic peptides — a new peptide biomarker for cardiopulmonary disease characterization.
Goetze, Jens Peter; Rehfeld, Jens F; Carlsen, Jørn; Videbaek, Regitze; Andersen, Claus B; Boesgaard, Soeren; Friis-Hansen, Lennart · Cross Sectional
RPEP-01306 · 2007Two neuropeptides — Substance P (SP) and CGRP — work together to drive airway inflammation. After ozone exposure in guinea pigs, both SP and CGRP increased with the same timing and location pattern, with a strong correlation between their expression levels.
Critically, CGRP was shown to upregulate the Substance P receptor (NK-1R) at both mRNA and protein levels in lung tissue. This means CGRP doesn't just cause inflammation on its own — it amplifies Substance P's inflammatory effects by increasing the number of receptors SP can activate. This upregulation was mediated through PKA, Calmodulin-dependent Kinase, and Tyrosine Protein Kinase pathways.
Wu, Hong; Guan, Chaxiang; Qin, Xiaoqun; Xiang, Yang; Qi, Mingming; Luo, Ziqiang; Zhang, Changqing · Preclinical
RPEP-01414 · 2008VIP gene expression was essential for normal pulmonary vascular regulation, with VIP knockout mice developing spontaneous pulmonary hypertension and vascular remodeling — establishing VIP as an endogenous protective factor against pulmonary vascular disease.
Said, Sami I · Animal Study
RPEP-02882 · 2016KL4 (sinapultide) is the first synthetic peptide designed to replace surfactant protein B in lung surfactant therapies. Its formulation, Surfaxin, demonstrated that synthetic peptide-based surfactants can replace animal-derived surfactants for treating respiratory distress syndromes and acute lung injury. Structural studies revealed KL4 has adaptive helical properties — its shape changes depending on lipid environment and pH — with a five-amino-acid repeat pattern that enables it to interact differently with various lipid layers.
This structural plasticity appears to be key to how KL4 helps form stable DPPC monolayers at the air-water interface in the lungs — the same function that natural surfactant protein B performs to keep lung air sacs from collapsing.
Braide-Moncoeur, Otonye; Tran, Nhi T; Long, Joanna R · Review
RPEP-04855 · 2020Neutrophils kill M. tuberculosis through antimicrobial peptides (alpha-defensins/HNPs), cytokine signaling, and neutrophil extracellular traps, but their excessive activation causes pathological inflammation and tissue damage.
Hilda, J Nancy; Das, Sulochana; Tripathy, Srikanth P; Hanna, Luke Elizabeth · Review
RPEP-04979 · 2020GHK-Cu inhibited pulmonary fibrosis by reducing TNF-α/IL-6, collagen deposition, and EMT progression through suppression of TGFβ1/Smad2/3 signaling and NF-κB, with Nrf2 pathway activation.
Ma, Wen-Hui; Li, Meng; Ma, Hai-Feng; Li, Wei; Liu, Li; Yin, Yan; Zhou, Xiao-Ming; Hou, Gang · Animal
RPEP-05037 · 2020GLP-1 receptor agonists upregulate mucin expression in airways via p38 MAPK, exacerbating emphysematous phenotypes in obstructive lung disease models.
Nohara, Hirofumi; Nakashima, Ryunosuke; Kamei, Shunsuke; Fujikawa, Haruka; Ueno-Shuto, Keiko; Kawakami, Taisei; Eto, Yuka; Suico, Mary Ann; Li, Jian-Dong; Kai, Hirofumi; Shuto, Tsuyoshi · Animal
RPEP-05386 · 2021GLP-1RA users had significantly fewer asthma exacerbations at 6 months compared to SGLT-2 inhibitors (IRR 2.98), DPP-4 inhibitors (IRR 2.45), sulfonylureas (IRR 1.83), and basal insulin (IRR 2.58), all with p<0.05.
Foer, Dinah; Beeler, Patrick E; Cui, Jing; Karlson, Elizabeth W; Bates, David W; Cahill, Katherine N · Retrospective Cohort
RPEP-05421 · 2021Bleomycin-induced pulmonary fibrosis in guinea pigs caused significantly increased expression of substance P, NK1R, CGRP, TRPA1, and TRPV1 in cough reflex pathways, all positively correlated with enhanced cough sensitivity to capsaicin challenge.
Guan, Mengyue; Ying, Sun; Wang, Yuguang · Preclinical Animal Study
RPEP-05457 · 2021GLP-1R agonist induced weight loss, suppressed eosinophilic inflammation, reduced AHR, decreased IL-4/5/33, and inhibited NLRP3 inflammasome activation (reduced NLRP3, caspase-1, IL-1β) in lung tissues of obese asthmatic mice.
Hur, Jung; Kang, Ji Young; Kim, Young Kyoon; Lee, Sook Young; Lee, Hwa Young · Preclinical Animal Study
RPEP-05664 · 2021LL-37 levels in nasal secretions were inversely associated with multiple measures of bronchiolitis severity. Higher LL-37 meant:
- Shorter hospitalization (rho = -0.340, p = 0.001)
- Less medication use (p = 0.001)
- Shorter oxygen supplementation (rho = -0.339, p = 0.001)
- Shorter IV fluid administration (rho = -0.323, p = 0.001)
These associations remained significant after adjusting for confounding factors like age and other variables.
Notably, serum vitamin D levels were not associated with nasal LL-37 levels, challenging the assumption that vitamin D drives LL-37 production in the airways. Beta-defensin-2 nasal levels also showed no connection to disease severity.
Papadaki, Maria; Marmarinos, Antonios; Tsolia, Maria; Gourgiotis, Dimitrios; Soldatou, Alexandra · Observational
RPEP-12894 · 2025Inhaled treprostinil improved BNP levels, tricuspid pressure gradient, and oxygen requirements in a patient with severe interstitial pneumonia and pulmonary hypertension.
Otsuka, Mitsuki; Sonoda, Shiro; Yamada, Takayuki; Aoki, Shotaro; Yasuda, Tomoka; Sawada, Atsushi; Shirai, Tsuyoshi; Tateishi, Tomoya; Furusawa, Haruhiko; Miyazaki, Yasunari · Case Report
RPEP-12903 · 2025Female COPD ICU patients had significantly higher rates of heart failure, obesity, and elevated BNP levels compared to males.
Ozdemir, Tarkan; Yıldız, Murat; Arı, Maşide; Arı, Emrah; Eraslan Doğanay, Güler; Cırık, Mustafa Özgür; Doğancı, Melek; Özdilekcan, Çiğdem; Kızılgöz, Derya; Şipit, Yusuf Tuğrul · Cross Sectional
RPEP-12909 · 2025About 50% of obese patients with OSA achieved resolution of their condition with tirzepatide over 52 weeks.
Pack, Allan; Grunstein, Ronald; Mokhlesi, Babak; Ryan, Silke; Schwab, Richard; Gozal, David · Review