Aims: Bombesin receptors (BB receptors) and/or bombesin related peptides are expressed in the lower urinary tract, though their function and distribution in different species is largely unknown. This study examines whether BB receptor agonists can contract bladder smooth muscle in rats, mice, pigs and humans.
Methods: Bladder strips were placed in tissue baths for in vitro contractility. Neuronally evoked contractions were elicited using electric field stimulation (EFS). Effects of the BB receptor agonists, neuromedin B (NMB; BB1 receptor agonist) and gastrin-releasing peptide (GRP; BB2 receptor agonist) on baseline tone and EFS-induced contractions were monitored.
Results: In rat and human bladder strips, NMB and GRP (10(-11)-10(-6)M) increased EFS-induced contractions in a concentration dependent manner. In these species, NMB and GRP also increased baseline tension. In mouse and pig bladder strips, NMB and GRP (10(-8)-3×10(-6)M) had no effects on either parameter.
Conclusions: These data suggest that bombesin receptors BB receptor 1 and/or BB receptor 2 increase bladder contractions in rat and human. The site of action of these receptors may be pre- and/or post-synaptic, increasing release of transmitters or enhancing smooth muscle excitability, respectively. Thus, BB1 receptor and/or BB2 receptor may offer therapeutic targets for voiding dysfunction associated with impaired bladder contractility; however, species differences must be considered when studying these receptors. Part of this work was published in an abstract form at the SFN meeting New Orleans, 2012.
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http://dx.doi.org/10.1016/j.npep.2013.08.003 | DOI Listing |
Theranostics
December 2024
Department of Nuclear Medicine, Inselspital, University of Bern, Bern, Switzerland.
Radiopharmaceutical therapy (RPT) is an emerging prostate cancer treatment that delivers radiation to specific molecules within the tumor microenvironment (TME), causing DNA damage and cell death. Given TME heterogeneity, it's crucial to explore RPT dosimetry and biological impacts at the cellular level. We integrated spatial transcriptomics (ST) with computational modeling to investigate the effects of RPT targeting prostate-specific membrane antigen (PSMA), fibroblast activation protein (FAP), and gastrin-releasing peptide receptor (GRPR) each labelled with beta-emitting lutetium-177 (Lu) and alpha-emitting actinium-225 (Ac).
View Article and Find Full Text PDFPharmaceutics
October 2024
Immunology and Molecular Oncology Diagnostics Unit, Veneto Institute of Oncology IOV-IRCCS, 35128 Padua, Italy.
Prostate cancer (PC) represents the second most diagnosed form of cancer in men on a global scale. Despite the theranostic efficacy of prostate-specific membrane antigen (PSMA) radioligands, there is a spectrum of PC disease in which PSMA expression is low or absent. The gastrin-releasing peptide receptor (GRPR), also known as the bombesin type 2 receptor, has been identified as a target in both the early and advanced stages of PC.
View Article and Find Full Text PDFSovrem Tekhnologii Med
November 2024
DSc, Leading Researcher, Laboratory for Peptide Drugs and Vaccines Development, S.P. Kapitsa Research Institute of Technology; Ulyanovsk State University, 42 Leo Tolstoy St., Ulyanovsk, 432017, Russia.
Unlabelled: Bombesin receptors on the cell surface are of great interest as a target for targeted cancer therapy. One of the strategies of targeting bombesin receptors involves the use of tropic short peptides. However, the main limitation for the wide application of peptides as drugs is their low stability due to their sensitivity to extreme conditions of the internal body environment such as temperature and action of enzymes.
View Article and Find Full Text PDFMol Pharm
December 2024
Department of Molecular Oncology, BC Cancer Research Institute, Vancouver, British Columbia V5Z 1L3, Canada.
The gastrin-releasing peptide receptor (GRPR) is overexpressed in a variety of cancers and represents a promising target for diagnosis and therapy. However, the extremely high accumulation in the pancreas observed for most of the clinically evaluated GRPR-targeted radiopharmaceuticals could limit their applications. In this study, we synthesized one GRPR antagonist (ProBOMB5) and two GRPR agonists (LW02056 and LW02057) by replacing the 4-thiazolidinecarboxylic acid (Thz) residue in our previously reported GRPR-targeted tracers with Pro.
View Article and Find Full Text PDFFront Nucl Med
September 2023
Radiochemical Studies Laboratory, Energy & Safety, Institute of Nuclear & Radiological Sciences & Technology (INRASTES), National Centre for Scientific Research (NCSR) "Demokritos", Athens, Greece.
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