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'-triphosphatt: (alpha beta meATP: and adenosine 5'-O-(2-thiodiphosphate) (ADP beta S) caused concentration-dependent increases in spontaneous firing rate, with EC(50) values of 41.8 and 1.7 mu M, 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 alpha beta meATP, ADP beta S produced further increases in the Bring rate of these neurons. The P2 antagonist, suramin, ablated responses to alpha beta meATP, but did not affect responses to ADP beta S, 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 alpha beta meATP. In conclusion, a subpopulation of rat medial vestibular neuronal responses mediated by both P2X and PZY 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. (C) 1997 IBRO.