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NEUROPHARMACOLOGY

Modulation of Synaptic Transmission to Second-Order Peripheral Chemoreceptor Neurons in Caudal Nucleus Tractus Solitarius by ₁-Adrenoreceptors

Department of Pharmacology, The University of Texas Health Science Center at San Antonio, San Antonio, Texas

Norepinephrine (NE) is an important neurotransmitter in central autonomic regulation. Peripheral chemoreceptor stimulation activates central noradrenergic structures. These structures innervate and therefore could modulate neurons in caudal nucleus tractus solitarius (cNTS), which receives the first central projections from peripheral chemoreceptors. However, the role of ₁-adrenoreceptors in synaptic transmission of peripheral chemoreceptor inputs in cNTS is unknown. We investigated the responses to activation of ₁-adrenoreceptors on glutamatergic and GABAergic inputs in NTS slices using whole-cell recording. Second-order neurons were identified by 1,1'-dilinoleyl-3,3,3',3'-tetra-methylindocarbocyanine, 4-chlorobenzenesulphonate (DiA) labeling of carotid bodies. Electrical stimulation of ipsilateral tractus solitarius was used to evoke excitatory postsynaptic currents (eEPSCs), whereas inhibitory postsynaptic currents were evoked (eIPSCs) by electrically stimulating NTS near the recorded neuron. Application of ₁-adrenoreceptor agonist phenylephrine (PE) at 20 µM significantly decreased amplitudes of eEPSCs (78 ± 1% of control; n = 16; p < 0.01), and it increased amplitudes of eIPSCs (120 ± 13% of control; n = 7; p < 0.01). Both effects were blocked by the ₁-adrenoreceptor antagonist prazosin at 10 µM. PE did not change holding current, input resistance, and current-voltage relationship in cNTS neurons. PE significantly changed paired pulse ratios of eEPSC/eIPSCs, increased the frequency of miniature IPSCs (329 ± 10% of control; n = 6; p < 0.05), but it decreased that of miniature EPSCs (69 ± 6% of control; n = 5; p < 0.01). PE-induced inhibition of eEPSCs was independent of N-methyl-D-aspartate or GABA_B receptors. These results suggest that activation of ₁-adrenoreceptors reduces excitatory and enhances inhibitory inputs to second-order peripheral chemoreceptor neurons in cNTS via a presynaptic mechanism. These actions result in the inhibition of synaptic transmission and could play a role in the autonomic responses to hypoxia.

Address correspondence to: Dr. Steve W. Mifflin, Department of Pharmacology, MSC 7764, The University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Dr., San Antonio, TX 78229-3900. E-mail: mifflin{at}uthscsa.edu

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