Effects of L-glutamate on the responses to nerve stimulation in rat isolated atria.

In rat atria isolated with their sympathetic fibres the chronotropic responses to nerve stimulation with pulses of 2 ms duration were reduced in a concentration-dependent manner by 10 microM to 1 mM L-glutamate (Glu) and by 0.01 to 1.00 microM (R,S)-3-hydroxy-5-methoxyloxasole-4-propionic acid (AMPA), whereas they were unaffected by other agonists of Glu receptors such as 1 microM to 1 mM N-methyl-D-aspartic acid (NMDA), 10 microM to 1 mM kainate and 1 to 100 microM (+/-)-2-amino-4-phosphonobutyric acid (AP4). The reductions in the atrial responses to nerve stimulation caused by Glu were not accompanied by alterations in either the basal efflux of [3H]noradrenaline or its overflow in response to the stimulation. The sensitivity of the atria to exogenous noradrenaline was not modified by either Glu or AMPA. The decreases in the chronotropic responses caused by Glu and by AMPA were prevented by both the non-selective Glu receptor antagonist, 100 microM kynurenic acid, and the selective AMPA receptor antagonist, 10 to 50 microM 6,7-dinitroquinoxaline-2,3-dione (DNQX). In addition, the adenosine receptor antagonist, 8-phenyltheophylline (10 microM), as well as the muscarinic acetylcholine receptor antagonist, atropine (3 microM), prevented the inhibitory effects of both Glu and AMPA on the chronotropic responses of rat isolated atria. Since both adenosine and acetylcholine are known to exert negative inotropic and chronotropic effects in cardiac tissues, it is proposed that Glu could contribute, through the interaction with receptors of the AMPA type, to facilitate the release of adenosine and acetylcholine from the atria.(ABSTRACT TRUNCATED AT 250 WORDS)

Different receptor subtypes mediate the dual presynaptic effects of 5-hydroxytryptamine on peripheral sympathetic neurones.

1. The aim of the present work was to characterize the presynaptic 5-HT receptors that mediate either the facilitation of the responses to nerve stimulation in the nictitating membrane of the cat or the inhibition of the responses to nerve stimulation in the guinea-pig atria. 2. In the nictitating membrane of the cat, the shift to the left in the frequency-response curves produced by 5-HT (0.1 microM) was prevented by the 5-HT3 receptor antagonists, metoclopramide (1 microM) and MDL 72222 (0.01 microM). 3. The facilitatory effect of 5-HT is also prevented by the 5-HT2 receptor antagonist, 0.01 microM ketanserin. Nevertheless, this drug reduced by itself the responses to both nerve stimulation and exogenous NA in the nictitating membrane. 4. In the guinea-pig isolated atria, the inhibitory effect of 5-HT on the chronotropic responses to cardioaccelerans nerve stimulation was mimicked by the mixed 5-HT1A + 5-HT1B + 5-HT1D receptor agonist 5-carboxamidotryptamine (5-CT 0.1 and 1 microM). The 5-HT1A receptor agonist 8-OH-DPAT (0.1 and 1 microM) did not modify the responses of the atria to the nerve stimulation. 5. The 5-HT2 receptor antagonists, ketanserin (0.01 and 0.1 microM) and cyproheptadine (1 microM), did not prevent the inhibitory effect of 5-HT in the guinea-pig atria. 6. The present results suggest that the facilitatory effects of 5-HT in the nictitating membrane of the cat are linked to the activation of 5-HT3 receptors whereas the inhibitory effects observed in the guinea-pig atria are mediated by 5-HT1-like receptors.