[Pyrimidine receptor function in the central nervous system].
A spectroscopic method, using fluorescent Ca2+, K+ and Na+ ion indicators in combination with the use of fast-kinetic techniques on the time scale of 0.00004-10 s has been applied to study mechanisms of P2 pyrimidoceptor-mediated signal transduction in brain homogenates. Effects of the known P2 receptor ligands (ATP, alpha, beta-methylene-ATP, UTP, UDP and uridine) and the P1 receptor ligand, adenosine, were compared by measuring the rates of transmembrane Ca2+, K+ and Na+ ion fluxes in resealed plasmalemma fragments and nerve endings from the rat cerebral cortex. In homogenates containing resealed plasmalemma fragments, uridine (0.03-30 microM), but not adenosine, activated two phases of Ca2+ ion influx with onsets of a few ms and hundred ms in a concentration-dependent manner. Also, the activation of the fast-phase Ca2+ ion response by ATP, UDP and alpha, beta-methylene-ATP whereas that of the slow-phase by UTP and UDP were observed with 3 microM concentration of these P2 receptor ligands. In homogenates containing resealed nerve endings, the fast-phase Ca2+ ion response to uridine was absent. UTP, but not uridine and UDP (3 microM), activated a fast K+ ion influx with onset of < 1 ms. Adenosine (3 microM) evoked a slow Na+ ion influx with onset of > 0.1 s whereas the influx of Na+ ion to uridine was detectable below 0.01 s. Both nucleotides, ATP and UTP (3 microM), activated fluctuations of transmembrane Na+ ion influx and efflux. By contrast, UDP caused efflux of Na+ ion in the subsecond range of time. Collectively these results suggest that transmembrane cation fluxes mediated by kinetically distinguishable P2U pyrimidoceptor subtypes are different.
Szárics
E
E
Magyar Tudományos Akadémia, Budapest.
Kovács
I
I
Kovács
R
R
Skuban
N
N
Kardos
J
J
D000818:Animals; D002462:Cell Membrane / Q000502:physiology; D002540:Cerebral Cortex / Q000502:physiology*; D011687:Purines / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology*; D051381:Rats; D011983:Receptors, Purinergic / Q000187:drug effects / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
D011687:Purines; D011743:Pyrimidines; D011983:Receptors, Purinergic