Reductions of 56Fe heavy-particle irradiation-induced deficits in striatal muscarinic receptor sensitivity by selective cross-activation/inhibition of second-messenger systems.
Recent experiments have revealed radiation-induced (600 MeV/u 56Fe energetic particles) losses of sensitivity of rodent neostriatal muscarinic receptors to stimulation by cholinergic agonists that appears as reductions in oxotremorine enhancement of K(+)-evoked dopamine release. These losses were postulated to be the result of radiation-induced alterations early in phosphoinositide-mediated signal transduction. Additional findings indicated that if the ligand-receptor-G protein interface was by passed no radiation deficits were seen. In the present study, radiation-induced deficits in K(+)-evoked dopamine release were examined in perifused striatal tissue obtained from rats exposed to 0, 0.1 or 1.0 Gy of 56Fe particles (600 MeV/u). Results showed that these deficits could be reduced by co-applying combinations of various pharmacological agents that were known to have differential effects on various second messengers such as 1,4,5-inositol-trisphosphate (IP3). Combinations included oxotremorine-carbachol, and either oxotremorine or carbachol with arginine vasopressin or arachidonic acid. These results are discussed in terms of putative radiation-induced changes in receptor-containing membranes which alter receptor-G protein coupling/uncoupling.
Department of Behavioral Sciences, Armed Forces Radiobiology Research Institute, Bethesda, Maryland 20889-5145.
J A
JA
Joseph
R
R
Villalobos-Molina
B M
BM
Rabin
T K
TK
Dalton
A
A
Harris
S
S
Kandasamy
D000704:Analysis of Variance; D000818:Animals; D016718:Arachidonic Acid / Q000494:pharmacology; D001127:Arginine Vasopressin / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology*; D003342:Corpus Striatum / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects*; D004298:Dopamine / Q000378:metabolism*; D066298:In Vitro Techniques; D007504:Iron Radioisotopes; D008297:Male; D010095:Oxotremorine / Q000494:pharmacology*; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects*; D015290:Second Messenger Systems; D014916:Whole-Body Irradiation
D007504:Iron Radioisotopes; D011976:Receptors, Muscarinic; D001127:Arginine Vasopressin; D016718:Arachidonic Acid; D010095:Oxotremorine; D011189:Potassium Chloride; D002217:Carbachol; D004298:Dopamine