Volatile Anesthetics Inhibit Calcitonin Gene-Related Peptide Receptor-Mediated Responses in Pithed Rats and Human Neuroblastoma Cells

Abstract

Calcitonin gene-related peptide (CGRP) has a potent vasodilatory effect that is mediated by specific receptors predominantly coupled to the activation of adenylate cyclase. The effects of volatile anesthetics on CGRP-induced vasodilation are unclear. We studied the effects of sevoflurane and isoflurane on CGRPinduced vasodilation in pithed rats and CGRP receptor-mediated responses in SK-N-MC cells, which are used as a model system to study the CGRP receptor and its downstream pathways. Male Wistar rats were pithed by inserting a stainless steel rod into the spinal cord. Mean arterial pressure (MAP) and cardiac output were maintained at approximately 100 mm Hg and 50 ml ⅐ min Ϫ1 , respectively, with continuous infusion of noradrenaline. After 30 min of inhalation of anesthetics, CGRP (0.1, 0.3, 1.0, and 3.0 g/kg) was administered intravenously. In SK-N-MC cells, CGRP-, forskolin-, or cholera toxin-induced cAMP production was measured with or without anesthetics using radioimmunoassays. CGRP receptor binding density and affinity for the agonist were determined with (2-[125 I]iodohystidyl 10 ) CGRP with or without the anesthetics. Sevoflurane (4%) and isoflurane (2%) significantly inhibited the decrease in MAP and systemic vascular resistance. Furthermore, both anesthetics significantly inhibited CGRP-but not forskolin-induced cAMP production. Sevoflurane (4%) and isoflurane (4%) significantly inhibited cholera toxin-induced cAMP production. Both anesthetics did not affect ligand binding. These data suggest that sevoflurane and isoflurane inhibit CGRP-induced vasodilation at the site between the CGRP receptor and adenylate cyclase activation. The inhibitory site of volatile anesthetics on the CGRP receptor-mediated response involves G s protein.

Amnestic Concentrations of Sevoflurane Inhibit Synaptic Plasticity of Hippocampal CA1 Neurons through γ-Aminobutyric Acid–mediated Mechanisms

“…To determine the actual aqueous concentrations of sevoflurane in the submerged recording chamber for each concentration used, aliquots of the solution were taken from the recording chamber and filled into airtight glass containers for gas chromatographic measurements as described previously. 20 Figure 1 shows the final aqueous sevoflurane concentrations in our recording condition (n ϭ 5, each). A strong positive correlation (r ϭ 0.99971) was observed; for example, 0.5, 2.8, and 5.0% of sevoflurane were actually 0.04, 0.23, and 0.41 mM, respectively.…”

Attenuation of Native Hyperpolarization-Activated, Cyclic Nucleotide-Gated Channel Function by the Volatile Anesthetic Sevoflurane in Mouse Thalamocortical Relay Neurons

“…In neurons of the dorsal hippocampus of rats, exposure to sevoflurane resulted in lower levels of cAMP compared to control conditions (Xiong et al, 2013). This reduction of cAMP might be mediated by an inhibitory effect of sevoflurane on adenylyl cyclase activity (Kuroda et al, 2004).…”