Prostaglandins of the E series (PGEs) have been detected in high quantities in inflamed tissues; when injected in the circulation that supplies the skin they cause inflammation and pain. Evidence of PGE sensitization of C-nociceptors (polymodals) already exists. The present work establishes that PGE1 has a wider sensitizing effect: when injected subdermally it affects mechanoreceptive elements as well. Of moderate-threshold, slow-adapting A delta mechanoreceptors isolated in the skin of the rat leg and responding to punctate stimulation, 79% were sensitized by PGE1 injections nearby (8--12 mm) as judged by their increased responses to innocuous stimulation (0.5--5 g delivered by a stylus with 0.5 mm tip diameter). Of such units, 10.5% were not sensitized and another 10.5% were inhibited or lost. Controls showed at most a small and transient increase immediately following the injection whereas the PGE1 effect lasted from between 30 min to 3 h or longer. These results are discussed in connection with mechanoreceptor sensitization by other pain-producing and irritant substances. At the receptor level, 'nociception' under abnormal conditions (e.g. inflammation) may not be solely mediated by unambiguously 'nociceptive' units; in such conditions a wider sensitization of receptive elements may be a contributing factor in hyperalgesic or hyperaesthetic phenomena.
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http://dx.doi.org/10.1016/0006-8993(82)90612-6 | DOI Listing |
Front Cell Dev Biol
July 2023
Department of Genetic Medicine and Development, University of Geneva, Geneva, Switzerland.
The sperm-specific channel CatSper (cation channel of sperm) controls the intracellular Ca concentration ([Ca]) and plays an essential role in sperm function. It is mainly activated by the steroid progesterone (P4) but is also promiscuously activated by a wide range of synthetic and physiological compounds. These compounds include diverse steroids whose action on the channel is so far still controversial.
View Article and Find Full Text PDFPLoS One
December 2022
Department of Pharmacology, Gifu University Graduate School of Medicine, Gifu, Japan.
Interleukin-6 (IL-6) is a pro-inflammatory and bone-resorptive cytokine that also regulates bone formation. We previously showed that prostaglandin E1 (PGE1) induces the synthesis of IL-6 by activating p44/p42 mitogen-activated protein kinase (MAPK), stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK), and p38 MAPK in osteoblast-like MC3T3-E1 cells. In the present study, we investigated whether heat shock protein 70 (HSP70), a molecular chaperone that coordinates protein folding and homeostasis, affects PGE1-stimulated IL-6 synthesis in MC3T3-E1 cells through the MAPK activation.
View Article and Find Full Text PDFPediatr Int
January 2022
Neonatal Intensive Care Unit, Neonatology Department, Centro Hospitalar Universitário de São João, Porto, Portugal.
ChemMedChem
August 2022
Department of Medicinal Chemistry and, Institute for Therapeutics Discovery and Development, College of Pharmacy, University of Minnesota, 717 Delaware Street, SE, Minneapolis, MN 55414, USA.
The cation channel of sperm (CatSper) is a validated target for nonhormonal male contraception, but it lacks selective blockers, hindering studies to establish its role in both motility and capacitation. Via an innovative calcium uptake assay utilizing human sperm we discovered novel inhibitors of CatSper function from a high-throughput screening campaign of 72,000 compounds. Preliminary SAR was established for seven hit series.
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