Differential role of ionotropic glutamatergic mechanisms in responses to NTS P(2x) and A(2a) receptor stimulation.

Activation of ATP P(2x) receptors in the subpostremal nucleus tractus solitarii (NTS) via microinjection of alpha,beta-methylene ATP (alpha,beta-MeATP) elicits fast initial depressor and sympathoinhibitory responses that are followed by slow, long-lasting inhibitory effects. Activation of NTS adenosine A(2a) receptors via microinjection of CGS-21680 elicits slow, long-lasting decreases in arterial pressure and renal sympathetic nerve activity (RSNA) and an increase in preganglionic adrenal sympathetic nerve activity (pre-ASNA). Both P(2x) and A(2a) receptors may operate via modulation of glutamate release from central neurons. We investigated whether intact glutamatergic transmission is necessary to mediate the responses to NTS P(2x) and A(2a) receptor stimulation. The hemodynamic and neural (RSNA and pre-ASNA) responses to microinjections of alpha,beta-MeATP (25 pmol/50 nl) and CGS-21680 (20 pmol/50 nl) were compared before and after pretreatment with kynurenate sodium (KYN; 4.4 nmol/100 nl) in chloralose-urethan-anesthetized male Sprague-Dawley rats. KYN virtually abolished the fast responses to alpha,beta-MeATP and tended to enhance the slow component of the neural responses. The depressor responses to CGS-21680 were mostly preserved after pretreatment with KYN, although the increase in pre-ASNA was reduced by one-half following the glutamatergic blockade. We conclude that the fast responses to stimulation of NTS P(2x) receptors are mediated via glutamatergic ionotropic mechanisms, whereas the slow responses to stimulation of NTS P(2x) and A(2a) receptors are mediated mostly via other neuromodulatory mechanisms.