抄録
L-DOPA is proposed to be a neurotransmitter of the primary baroreceptor afferents terminating in NITS, whereas GABA inhibits baroreflex within NTS. Thus, if our proposal is truly the case, GABA should tonically inhibit pre and/or post-synaptic DOPAergic functions in NTS. Muscimol 10 and 30 μM, locally perfused via probes, inhibited DOPA release by 50 and 60% during microdialysis of NTS in anesthetized rats, with a peak 2 hr after perfusion. Muscimol (10 μM)-induced inhibition was antagonized by noneffectivel0 μM bicuculline. Bicuculline 30 μM alone increased DOPA release in a similar time course. By microinjections into depressor sites of NTS, DOPA 10-60 ng or GABA 3-300 ng elicited dose-dependent hypotension or hypertension. Cardiodepressor responses to DOPA 30 ng were dose-dependently reduced by prior injections of GABA 3-30 ng, also by nipecotic acid 100 ng, but inversely potentiated by bicuculline 10 ng, when respective regulatory response to GABA-related drug returned to control. Meanwhile, DOPA methyl ester, a competitive DOPA antagonist, did not displace [3H]-GABA binding in brain membrane preparations. When a tonic function of endogenously released DOPA was antagonized by this antagonist 1 μg microinjected 1 min previously, cardiopressor responses to GABA 300 ng were reduced by a half. DOPA 10 nM evoked GABA by 40% in the first 20 min sample. Under inhibition of central AADC by perfusion of NSD-1015 200 μM, DOPA 1-100 nM concentration-dependently evoked GABA by 35-60%. DOPA (10 nM)-induced GABA release was not mimicked by dopamine or D-DOPA 10 nM, but was abolished by Ca2+ deprivation or perfusion of tetrodotoxin 1μM. GABA seems to inhibit tonically via activation of GABAA receptors presynaptic DOPA release and postsynaptic depressor and bradycardic responses to DOPA and to induce hypertension and tachycardia in part via inhibition of tonic postsynaptic cardiodepressor function of endogenously released DOPA within NTS. DOPA seems to evoke by itself endogenous GABA from GABAergic neurons as a compensatory mechanism of baroreflex within NTS. These findings further support the idea that DOPA is a neurotransmitter of the primary baroreceptor afferents terminating in rat NTS.
