Functional evidence for multiple purinoceptor subtypes in the rat medial vestibular nucleus

Abstract

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 α,β-methyleneadenosine 5′-triphosphate and adenosine 5′- O-(2-thiodiphosphate) caused concentration-dependent increases in spontaneous firing rate, with ec 50 values of 1.7 and 41.8 μM, 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 α,β-methyleneadenosine 5′-triphosphate, adenosine 5′- O-(2-thiodiphosphate) produced further increases in the firing rate of these neurons. The P2 antagonist, suramin, ablated responses to α,β-methyleneadenosine 5′-triphosphate, but did not affect responses to adenosine 5′- O-(2-thiodiphosphate), whereas pyridoxal-phosphate-6-azophenyl-2′,4′-disulphonic acid antagonized responses to both agonists. The nucleotide analogue α,β-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 α,β-methyleneadenosine 5′-triphosphate. In conclusion, a subpopulation of rat medial vestibular neuronal responses mediated by both P2X and P2Y purinoceptors can be distinguished, in addition to the presence of P1 receptors for adenosine. Comparison of these P2 purinoceptors with the properties of recombinantly expressed P2X and P2Y receptors suggests that these endogenous P2 purinoceptors differ in several important aspects from heterologously expressed recombinant receptors identified from cloning studies.