Presynaptic histamine H1 and H3 receptors modulate sympathetic ganglionic synaptic transmission in the guinea-pig

1. To study the effects of histamine on the efficacy of sympathetic ganglionic synaptic transmission, extracellular recordings of the postganglionic compound action potential (CAP) and intracellular recordings of excitatory postsynaptic potentials (EPSPs) elicited by preganglionic electrical stimulation were obtained from isolated guinea-pig superior cervical ganglia (SCG). 2. In different preparations, superfusion with histamine (0.1-100 microM) either potentiated or depressed the postganglionic CAP elicited by electrical stimulation of the cervical sympathetic trunk (0.2-3.0 Hz). The direction of response produced by histamine did not depend on stimulation frequency or histamine concentration; potentiation and depression both showed concentration dependence over the range of histamine concentrations tested. 3. Experiments employing a variety of histamine receptor agonists or antagonists revealed that histamine-induced potentiation of the postganglionic CAP could be attributed to histamine H1 receptor activation, and depression to H3 receptor activation. 4. Histamine similarly potentiated or depressed the intracellularly recorded EPSP. However, these opposite effects occurred at different synapses. In agreement with the studies on the postganglionic CAP, histamine H1 antagonists prevented histamine-induced potentiation of the EPSP and H3 receptor antagonists prevented histamine-induced depression. 5. Direct quantal analyses of histamine-induced synaptic potentiation and depression were implemented to determine the pre- and postsynaptic components of these effects. Quantal size was estimated by measuring the amplitude of spontaneous miniature EPSP amplitudes. Histamine-induced potentiation and depression of the evoked EPSP were found to be accompanied by increased or decreased quantal content respectively, and unchanged quantal size, providing evidence that presynaptic mechanisms were involved in mediating both effects. 6. Some guinea-pigs were actively sensitized to ovalbumin. Subsequent exposure of the isolated SCG from these animals to the sensitizing antigen produced changes in the EPSP amplitude that correlated significantly to the response produced by exogenously applied histamine at the same synapse. 7. The correspondence between the effects of specific antigen challenge and exogenous histamine on evoked EPSPs at a synapse provides evidence that endogenous histamine released during an immunological response to antigen challenge can activate histamine H1 and H3 receptors to modulate synaptic efficacy in sympathetic ganglia.