Linked Life Data

19077126

Source:http://linkedlifedata.com/resource/pubmed/id/19077126

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2009-1-5
pubmed:abstractText
Opioids are known to control the activity of P2X receptors in the sensory neurons of rats. These receptors are important in persistent pain signaling. However, there are extremely severe pain states, such as those associated with metastatic diseases, that are refractory to opioid treatment. We have tested the possibility that cancer cells affect the sensitivity of P2X(2/3) and P2X(2) receptors to opiates. The sensitivity of ATP-activated currents to the selective mu-opioid receptor agonist endomorphin-1 was evaluated in rat nodose neurons co-cultured (on separate coverslips) with fibrosarcoma cells (NCTC 2472) using whole-cell patch-clamp recordings. Both in control and in co-cultured neurons, P2X-mediated responses exhibited highly variable biphasic desensitization kinetics with fast and slow components. However, ATP-activated currents in co-cultured neurons acquired a new feature: the degree of their inhibition by endomorphin-1 demonstrated strong dependence on their desensitization kinetics. The neurons with 'slower' responses were subject to a smaller inhibitory effect of the opioid. The 'ultra-slow' responses completely lost their sensitivity to the opioid. The occurrence of such responses, rarely observed in the control neurons, was considerably increased with the duration of co-culturing. Application of endomorphin-1 to nodose neurons, co-cultured with rapidly proliferating but non-malignant cells (fibroblasts), resulted in data similar to those for the control. In summary, fibrosarcoma cells release diffusible factors altering the properties of desensitization kinetics of P2X receptors and, in particular, decrease their sensitivity to opioid inhibitory control. These phenomena may increase neuronal excitability initiated by peripheral ATP release and thereby contribute to the decreased sensitivity of cancer pain to opioids.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
1460-9568
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
29
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
76-86
pubmed:dateRevised
2011-6-16
pubmed:meshHeading
pubmed-meshheading:19077126-Adenosine Triphosphate, pubmed-meshheading:19077126-Analgesics, Opioid, pubmed-meshheading:19077126-Animals, pubmed-meshheading:19077126-Cell Culture Techniques, pubmed-meshheading:19077126-Cell Line, Tumor, pubmed-meshheading:19077126-Cells, Cultured, pubmed-meshheading:19077126-Coculture Techniques, pubmed-meshheading:19077126-Down-Regulation, pubmed-meshheading:19077126-Drug Resistance, pubmed-meshheading:19077126-Fibrosarcoma, pubmed-meshheading:19077126-Kinetics, pubmed-meshheading:19077126-Membrane Potentials, pubmed-meshheading:19077126-Neoplasms, pubmed-meshheading:19077126-Nociceptors, pubmed-meshheading:19077126-Nodose Ganglion, pubmed-meshheading:19077126-Oligopeptides, pubmed-meshheading:19077126-Patch-Clamp Techniques, pubmed-meshheading:19077126-Rats, pubmed-meshheading:19077126-Rats, Wistar, pubmed-meshheading:19077126-Receptors, Opioid, mu, pubmed-meshheading:19077126-Receptors, Purinergic P2, pubmed-meshheading:19077126-Receptors, Purinergic P2X, pubmed-meshheading:19077126-Sensory Receptor Cells, pubmed-meshheading:19077126-Time Factors
pubmed:year
2009
pubmed:articleTitle
P2X receptors in sensory neurons co-cultured with cancer cells exhibit a decrease in opioid sensitivity.
pubmed:affiliation
Bogomoletz Institute of Physiology, Ukraine Bogomoletz Institute of Physiology, Kiev, Ukraine.
pubmed:publicationType
Journal Article, In Vitro, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural