Brain research bulletin
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Brain research bulletin · Mar 2001
Spider neurotoxins block the beta scorpion toxin-induced calcium uptake in rat brain cortical synaptosomes.
In this paper we describe the effects of the beta scorpion toxin Tityus gamma (TiTX gamma) and spider neurotoxins Tx3-3 and Tx3-4 in the (45)Ca(2+) uptake in synaptosomes. The TiTX gamma-stimulatory effect on (45)Ca(2+) uptake in synaptosomes was inhibited omega-Conotoxin MVIIC (omega-CgTX MVIIC) (0.1 microM) and omega-Agatoxin IVA (0.1 microM) by 70% and 41%, respectively. omega-CgTX MVIIC (1.0 microM) almost completely blocked the TiTX gamma-induced (45)Ca(2+) uptake in synaptosomes. ⋯ The spider neurotoxins Tx3-3 and Tx3-4 inhibited the TiTX gamma-induced calcium uptake with an IC(50) of 10.0 and 30.0 nM, respectively. It is suggested that spider neurotoxins Tx3-3 and Tx3-4 blocking effect in the TiTX gamma-induced calcium uptake involves P/Q-type calcium channels.
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Brain research bulletin · Jan 2001
Microinjection of a 5-HT3 receptor agonist into the NTS of awake rats inhibits the bradycardic response to activation of the von Bezold-Jarisch reflex.
In the present study we investigated the effects of bilateral microinjection into the lateral commissural nucleus tractus solitarius (NTS) of 2-methyl-5-HT, a 5-HT3 receptor agonist, on the bradycardic response of the von Bezold-Jarisch reflex of awake rats. We evaluated mainly the bradycardic response because in previous studies we documented that the hypotensive response of the von-Bezold-Jarisch reflex in awake rats is secondary to the intense bradycardic response. ⋯ Microinjections of 2-methyl-5-HT into the NTS produced a significant increase in basal mean arterial pressure [(MAP), 97 +/- 4 vs. 114 +/- 4 mmHg), no changes in basal heart rate and a significant reduction in bradycardic (-78 +/- 19; -94 +/- 24 and -107 +/- 21 bpm) and hypotensive (-16 +/- 4; -10 +/- 5 and -17 +/- 4 mmHg) responses to activation of the von Bezold-Jarisch reflex at 3, 10 and 20 min, respectively, when compared with the control value (-231 +/- 13 bpm and -43 +/- 4 mmHg). The data of the present study suggest that serotonin acting on 5-HT3 receptors in the NTS may play an important inhibitory neuromodulatory role in the bradycardic response to activation of the von Bezold-Jarisch reflex.
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Brain research bulletin · Dec 2000
Role of altered cyclooxygenase metabolism in impaired cerebrovasodilation to nociceptin/orphanin FQ following brain injury.
This study was designed to determine the role of altered cyclooxygenase metabolism in impaired pial artery dilation to the newly described opioid, nociceptin orphanin FQ (NOC/oFQ), following fluid percussion brain injury (FPI) in newborn pigs equipped with a closed cranial window. Recent studies show that NOC/oFQ contributes to oxygen free radical generation observed post FPI in a cyclooxygenase dependent manner. FPI was produced by using a pendulum to strike a piston on a saline filled cylinder that was fluid coupled to the brain via a hollow screw inserted through the cranium. ⋯ NOC/oFQ (10(-8), 10(-6) M) induced pial artery dilation that was reversed to vasoconstriction by FPI while the cyclooxygenase inhibitor indomethacin (5 mg/kg, intravenous) partially restored such vascular responses (8 +/- 1 and 15 +/- 1 vs. -7 +/- 1 and -12 +/- 1 vs. 7 +/- 1 and 12 +/- 1% for 10(-8), 10(-6) M NOC/oFQ in sham, FPI and FPI-Indo pretreated animals). Similar observations were made in FPI animals pretreated with the thromboxane receptor antagonist SQ 29,548 or the free radical scavenger polyethylene glycol superoxide dismutase and catalase. These data indicate that altered NOC/oFQ induced cyclooxygenase metabolism contributes to impairment of dilation to this opioid following FPI.
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Brain research bulletin · Sep 2000
Large cortical lesions produce enduring forelimb placing deficits in un-treated rats and treatment with NMDA antagonists or anti-oxidant drugs induces behavioral recovery.
Previous studies have utilized a lesion model of cortical injury that produces transient behavioral impairments to investigate the recovery of function process. To better understand the recovery process, it would be beneficial to use a lesion model that produces more severe, enduring, behavioral impairments. The purpose of experiment 1 was to validate whether large lesions of the sensorimotor cortex (SMC), which included the rostral forelimb and caudal forelimb regions, produced enduring behavioral deficits. ⋯ Treatment with these drugs induced behavioral recovery on the forelimb placing tests, whereas, the saline-treated rats did not show any signs of behavioral recovery for at least 3 months. Anatomical analysis of the striatum showed that MK-801 and MgCl(2) but not PBN reduced the extent of lesion-induced striatal atrophy. These results suggest that administration of MK-801, MgCl(2), or PBN shortly after cortical injury can induce recovery of function when recovery is otherwise not expected in un-treated rats.
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Brain research bulletin · Jul 2000
Ketamine blockage of both tetrodotoxin (TTX)-sensitive and TTX-resistant sodium channels of rat dorsal root ganglion neurons.
Ketamine, a general anesthetic, has been reported to block sodium channels. Two types of Na(+) channels, tetrodotoxin (TTX)-sensitive (TTX-s) and TTX-resistant (TTX-r), are expressed in dorsal root ganglion (DRG) neurons. The present study was to investigate the effects of ketamine on both types, particularly on TTX-r channels, using whole-cell patch-clamp recordings in dissociated rat DRG neurons. ⋯ Activation and inactivation properties of both TTX-s and TTX-r Na(+) channels were affected by ketamine. Since TTX-r Na(+) channels were preferentially expressed in small DRG neurons known as nociceptors, blockage of TTX-r Na(+) channels by ketamine may result in reducing nociceptive signals conducting to the spinal cord. Moreover, both TTX-r and TTX-s Na(+) channels would be non-selectively blocked by ketamine at high concentration, suggesting that the high dose of ketamine might produce an action of local anesthesia.