Functional evidence for multiple purinoceptor subtypes in the rat medial vestibular nucleus.
Extracellular recording techniques were used in brain slices to characterize excitatory responses produced by purine nucleotides in the rat medial vestibular nucleus, an area where functional purinoceptors have not previously been described. In the continued presence of the adenosine antagonist 8-cyclopentyl-1,3-dipropylxanthine, which alone caused a small increase in the spontaneous firing rate, the P2 purinoceptor agonists alpha,beta-methyleneadenosine 5'-triphosphate (alphabeta meATP) and adenosine 5'-O-(2-thiodiphosphate) (ADPbetaS) caused concentration-dependent increases in spontaneous firing rate, with EC50 values of 41.8 and 1.7 microM, respectively. Only approximately 35% of all neurons studied displayed excitatory responses to these agents. Responses waned in the continued presence of high concentrations of the latter, but not the former agonist. Furthermore, in the continued presence of a maximal concentration of alphabeta meATP, ADPbetaS produced further increases in the firing rate of these neurons. The P2 antagonist, suramin, ablated responses to alphabeta meATP, but did not affect responses to ADPbetaS, whereas pyridoxal-phosphate-6-azophenyl-2',4'-disulphonic acid antagonized responses to both agonists. The nucleotide analogue alpha,beta-methyleneadenosine 5'-diphosphate, which displays affinity for putative P2X receptors in brain, also produced concentration-dependent increases in firing frequency, which were also markedly antagonized in the presence of suramin, this agonist being only slightly less potent than alphabeta meATP. In conclusion, a subpopulation of rat medial vestibular neuronal responses mediated by both P2X and P2Y purinoceptors can be distinguished. Comparison of their properties with those of recombinantly expressed P2X and P2Y receptors suggests that these endogenous P2 purinoceptor types differ in several important aspects from heterologously expressed recombinant receptors identified from cloning studies.
Chessell
I P
IP
Glaxo Institute of Applied Pharmacology, University of Cambridge, U.K.
Michel
A D
AD
Humphrey
P P
PP
D000244:Adenosine Diphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000818:Animals; D005071:Evoked Potentials / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D011732:Pyridoxal Phosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018048:Receptors, Purinergic P2 / Q000187:drug effects / Q000502:physiology*; D058476:Receptors, Purinergic P2X2; D013806:Theophylline / Q000031:analogs & derivatives / Q000494:pharmacology; D013873:Thionucleotides / Q000494:pharmacology; D013997:Time Factors; D014726:Vestibular Nuclei / Q000502:physiology*
C546403:P2rx2 protein, rat; D018048:Receptors, Purinergic P2; D058476:Receptors, Purinergic P2X2; D013873:Thionucleotides; C077792:pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid; C030812:adenosine 5'-O-(2-thiodiphosphate); C053907:8-cyclopentyl-1,3-dimethylxanthine; D011732:Pyridoxal Phosphate; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D013806:Theophylline; C002630:alpha,beta-methyleneadenosine 5'-triphosphate; C008501:2-methylthio-ATP