Anesthesia and analgesia
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Anesthesia and analgesia · May 2004
Metoclopramide causes airway smooth muscle relaxation through inhibition of muscarinic M3 receptor in the rat trachea.
Although metoclopramide, often used as an antiemetic, is reported to have an anticholinesterase action, the effect on airway smooth muscle remains unclear. We investigated the effect of metoclopramide on the contraction, phosphatidylinositol response, and binding affinity of muscarinic M(3) receptors in rat trachea preparations. Male Wistar rats were anesthetized and their tracheas excised and chopped into 3-mm-wide rings, 1-mm-wide slices, or frozen 10- microm-thick sections. Contraction was induced with 0.55 microM carbachol (CCh) and, 30 min later, metoclopramide (10 microM to 1 mM) was added. The slices were incubated with (3)[H]myo-inositol, 0.55 microM CCh, and metoclopramide, and the formation of (3)[H] inositol monophosphate was measured. A radioligand binding study was conducted to examine the effects of metoclopramide using [(3)H] 4-diphenylacetoxy-N-methyl-piperidine methobromide (4-DAMP), a muscarinic M(3) receptor antagonist, in sections of the trachea. Metoclopramide concentration dependently attenuated CCh-induced contraction and inositol monophosphate accumulation, and also attenuated the binding affinity of 4-DAMP to muscarinic M(3) receptors. The 50% inhibitory concentration of metoclopramide against the binding affinity of 4-DAMP to muscarinic M(3) receptors of rat trachea was 24 micro M. These findings suggest that the attenuation by metoclopramide of CCh-induced contraction and phosphatidylinositol response may be mediated through the muscarinic M(3) receptors. ⋯ We investigated the effect of metoclopramide on the contraction, phosphatidylinositol response, and binding affinity of muscarinic M(3) receptors in rat trachea preparations. Our findings suggest that the attenuation by metoclopramide of carbachol-induced contraction and phosphatidylinositol response may be mediated through the muscarinic M(3) receptors.
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Anesthesia and analgesia · May 2004
The interaction between gamma-aminobutyric acid agonists and diltiazem in visceral antinociception in rats.
To examine whether the gamma-aminobutyric acid (GABA) receptor agonists and L-type voltage-dependent calcium channel blockers potentiate each other on the visceral antinociceptive effects at the spinal cord, we assessed visceral nociception with colorectal distension (CD) test in rats with an intrathecal catheter. The measurements were performed after intrathecal administration of a GABA agonist (muscimol or baclofen), a calcium channel blocker (diltiazem), or the combination of the two. CD threshold did not change after muscimol 0.1 microg, baclofen 0.01 microg, or diltiazem 100 microg, but increased slightly after muscimol 1 microg and baclofen 0.1 microg. When muscimol 0.1 microg or 1 microg was administered with diltiazem, the increase in CD threshold was significantly larger than muscimol alone (at 5 min, 26.2% versus 0.6% MPE (maximum possible effect) or 84.5% versus 19.5%MPE, respectively; P < 0.01). The CD threshold after the combination of baclofen 0.1 microg and diltiazem also showed a significantly larger increase than that seen after baclofen alone (at 5 min, 48.0% versus 14.3% MPE; P < 0.01). Motor paralysis observed with muscimol 1 microg did not increase when muscimol was coadministered with diltiazem. In conclusion, intrathecal diltiazem in combination with a GABA agonist, muscimol or baclofen, potentiated the GABA agonists-induced visceral antinociception without increasing motor paralysis. ⋯ Intrathecal administration of diltiazem in combination with a gamma-aminobutyric acid (GABA) agonist, muscimol or baclofen, potentiated the GABA agonists-induced visceral antinociception but did not affect motor paralysis. The present results indicate that the coadministration of the two types of drugs may be clinically useful.
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Anesthesia and analgesia · May 2004
The inhibitory effects of tramadol on 5-hydroxytryptamine type 2C receptors expressed in Xenopus oocytes.
Although tramadol is widely available as an analgesic, its mechanism of antinociception remains unresolved. Serotonin (5-hydroxytryptamine, 5-HT) is a monoaminergic neurotransmitter that modulates numerous sensory, motor, and behavioral processes. The 5-HT type 2C receptor (5-HT(2C)R) is one of the major 5-HT receptor subtypes and is implicated in many important effects of 5-HT, including pain, feeding, and locomotion. In this study, we used a whole-cell voltage clamp to examine the effects of tramadol on 5-HT-induced Ca(2+)-activated Cl(-) currents mediated by 5-HT(2C)R expressed in Xenopus oocytes. Tramadol inhibited 5-HT-induced Cl(-) currents at pharmacologically relevant concentrations. The protein kinase C (PKC) inhibitor, bisindolylmaleimide I (GF109203x), did not abolish the inhibitory effects of tramadol on the 5-HT(2C)R-mediated events. We also studied the effects of tramadol on [(3)H]5-HT binding to 5-HT(2C)R expressed in Xenopus oocytes, and found that it inhibited the specific binding of [(3)H]5-HT to 5-HT(2C)R. Scatchard analysis of [(3)H]5-HT binding revealed that tramadol altered the apparent dissociation constant for binding without changing maximal binding, indicating competitive inhibition. The results suggest that tramadol inhibits 5-HT(2C)R function, and the mechanism of this inhibitory effect seems to involve competitive displacement of the 5-HT binding to the 5-HT(2C)R, rather than via activation of the PKC pathway. ⋯ We examined the effects of tramadol on 5-hydroxytryptamine type 2C receptor (5-HT(2C)R) expressed in Xenopus oocytes. Tramadol inhibited 5-HT(2C)R function and the specific binding of [(3)H]5-HT to 5-HT(2C)R in a competitive manner. From these data, the mechanism of the inhibitory effect on 5-HT(2C)R might involve the competitive displacement of 5-HT binding to the 5-HT(2C)R.
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Anesthesia and analgesia · May 2004
Letter Case ReportsAn unusual cause of intraoperative shivering.