Pentobarbital inhibits glucose uptake, but not water transport by glucose transporter type 3.

To understand the mechanisms underlying the neuroprotective efficacy of barbiturates, the effect of pentobarbital on glucose uptake and water transport was determined in Xenopus oocytes expressing glucose transporter type 3 (GLUT3). Pentobarbital induced a 50% concentration-dependent inhibition in glucose uptake, but exerted no effect on water transport by GLUT3. Eadie-Hofstee analysis showed that pentobarbital decreased Vmax significantly, but not Km of GLUT3 for 2-deoxy-D-glucose. Although the protein kinase C (PKC) activator significantly decreased glucose uptake by GLUT3, no additive or synergistic interactions were observed between the PKC activator and pentobarbital. Our results suggest that pentobarbital may play an important role in neuroprotection by inhibition of glucose uptake by GLUT3 by a mechanism involving PKC.

Effects of ketamine on glucose uptake by glucose transporter type 3 expressed in Xenopus oocytes: The role of protein kinase C.

We investigated the effects of ketamine on the type 3 facilitative glucose transporter (GLUT3), which plays a major role in glucose transport across the plasma membrane of neurons. Human-cloned GLUT3 was expressed in Xenopus oocytes by injection of GLUT3 mRNA. GLUT3-mediated glucose uptake was examined by measuring oocyte radioactivity following incubation with 2-deoxy-d-[1,2-(3)H]glucose. While ketamine and S(+)-ketamine significantly increased GLUT3-mediated glucose uptake, this effect was biphasic such that higher concentrations of ketamine inhibited glucose uptake. Ketamine (10microM) significantly increased V(max) but not K(m) of GLUT3 for 2-deoxy-d-glucose. Although staurosporine (a protein kinase C inhibitor) increased glucose uptake, no additive or synergistic interactions were observed between staurosporine and racemic ketamine or S(+)-ketamine. Treatment with ketamine or S(+)-ketamine partially prevented GLUT3 inhibition by the protein kinase C activator phorbol-12-myrisate-13-acetate. Our results indicate that ketamine increases GLUT3 activity at clinically relevant doses through a mechanism involving PKC inhibition.

Effects of prostaglandin E1 on vascular ATP-sensitive potassium channels.

BACKGROUND: Prostaglandin E1 (PGE1) has been reported to activate ATP-sensitive potassium (KATP) channels, which induces vasorelaxation. However, direct evidence of PGE1 interactions with vascular KATP channels is limited. METHODS: The present study investigated the effects and mechanisms of PGE1 on vascular KATP channels in both isometric tension and patch clamp experiments. Isometric tension experiments were performed in rat thoracic aortic rings without an endothelium. Electrophysiologic experiments were performed using patch-clamp techniques to monitor KATP channels in rat vascular smooth muscle cells. RESULTS: PGE1 significantly decreased the isometric tension in a concentration-dependent manner, which was partially inhibited by pretreating with a KATP channel inhibitor, glibenclamide (1 microM), or an inhibitor of protein kinase A (PKA), Rp-cAMPS (100 microM). Application of PGE1 to the bath solution during cell-attached recordings induced a significant increase in KATP channel activity, whereas PGE1 failed to activate KATP channels in the inside-out patches. The PGE1-induced KATP channel currents in cell-attached patches were abolished by pretreating with Rp-cAMPS (100 microM). CONCLUSIONS: The results indicate that the activation of vascular KATP channels played an important role in the PKA-dependent PGE1-induced vasorelaxation. Furthermore, an electrophysiological experiment demonstrated that PGE1 activated vascular KATP channels via PKA activation.

[Anesthetic management of a patient with mental disabilities as well as the past history of heat stroke and neuroleptic malignant syndrome].

A 22-year-old man with mental disabilities with the history of neuroleptic malignant syndrome and heat stroke was scheduled for dental treatment under general anesthesia. Heat stroke and neuroleptic malignant syndrome are related to malignant hyperthermia. We suggested the patient and family to undergo preoperative screening tests for malignant hyperthermia susceptibility, but they rejected. We selected slow induction using nitrous oxide, oxygen and sevoflurane to prevent excitement and anxiety for placing a catheter in a peripheral vein. We were very cautious in primary symptoms of malignant hyperthermia, i.e., tachycardia, increased end-tidal carbon dioxide, and rigidity of masseter. In the perioperative period, no complications occurred.

[Anesthetic management of a teenage athlete who developed arrhythmia during general anesthesia].

A 17-year-old man with fracture of the mandible underwent open fixation under general anesthesia. He was an athlete of the rugby suffering the fracture in a match. His preoperative physical examinations were normal except for I degrees atrioventricular block on electrocardiogram (ECG). During anesthesia, atrioventricular dissociation and frequent premature ventricular contractions were induced by the stimulation of nasotracheal intubation and the administration of atropine for the reversal of muscle relaxation. We thought the cause of the arrhythmia is the athlete's heart which may be vagotonic and may induce vagal reflex or fatal arrhythmia. This case demonstrates that it is necessary to pay attention to chronotropic action associated with the intubation of nasopharynx, the handling of laryngoscope and the usage of drugs for the anesthetic management of the athlete.

[Effects of propofol and thiamylal on nicorandil induced ATP-sensitive potassium channel activities in cultured rat aortic smooth muscle cells].

BACKGROUND: Nicorandil, a hybrid ATP-sensitive potassium (K(ATP)) channel opener and nitrate compound, is used clinically for the treatment of angina pectoris. In the present study, we investigated the effects of propofol and thiamylal on sarcolemmal K(ATP) channels activities induced by nicorandil in cultured rat aortic smooth muscle cells. METHODS: We used inside-out patch clamp configurations to investigate the effects of propofol and thiamylal on nicorandil induced K(ATP) channel activities. RESULTS: K(ATP) channel was not spontaneously activated by patch excision in the absence of intracellular ATP. Application of nicorandil (100 microM) induced a marked activation of KATP channel currents, which was completely blocked by 3 microM glibenclamide, the sulfonylurea that blocks K(ATP) channels. Nicorandil induced KATP channel currents were not significantly inhibited by application of 10 and 100 microM propofol to intracellular surface. However, application of 100 and 300 microM thiamylal to intracellular surface significantly inhibited the nicorandil induced K(ATP) channel currents, with relative channel activities decreasing to 0.65 +/- 0.08 and 0.46 +/- 0.10 of control, respectively. CONCLUSIONS: Propofol had no effect on nicorandil induced sarcolemmal KATP channel activities in rat aortic smooth muscle cells, whereas thiamylal significantly inhibited these channel activities at clinically relevant concentrations.

Characteristics of the trigeminal depressor response in cats.

We studied the effects of electrical stimulation of the inferior alveolar nerve (IAN) on cardiovascular responses in cats. There was statistical correlation between cardiovascular response and prestimulus mean arterial blood pressure (MABP) and heart rate (HR). A trigeminal depressor response (TDR) was induced when the prestimulus MABP and HR were above 95 mm Hg and 140 beats/min, respectively. We investigated further to identify the vasomotor regulating center and neural transmitters involved in TDR. In the medulla, electrical stimulation of the dorsomedial medulla, the infratrigeminal nucleus (IFT), and the rostral ventrolateral medulla (RVLM) induced a vasopressor response. We confirmed that neurons in the RVLM were retrogradely labeled by wheat germ agglutinin-conjugated horseradish peroxidase injection into the nucleus intermediolateralis of the spinal cord. The vasopressor response induced by IFT stimulation was similar to that induced by IAN stimulation. Vasodepressor responses were induced when the caudal ventrolateral medulla, the nucleus tractus solitarius, the lateral tegmental field, the trigeminal nucleus interpolaris, the trigeminal spinal tract, and the paramedian reticular nucleus were stimulated. These responses, however, were not similar to the vasodepressor response induced by IAN stimulation but were similar to the cardiovascular response induced by vagal afferent stimulation. After spinalization or lesion of the RVLM, MABP and HR decreased and TDR completely disappeared. Inhibitory synaptic ligands and receptors were localized using immunohistochemical techniques. Neurons immunopositive for adrenaline, noradrenaline, and gamma-aminobutyric acid (GABA), and adrenaline alpha(2A), GABA(A), GABA(B), and glycine receptors were distributed along the sympatho-reflexive route including the RVLM and IFT. These results suggest that TDR could be induced as negative feedback to sympathetic hyperactivity whenever MABP and HR are high, because of the inhibitory control of the RVLM.