Biomedical subjects

K Sumikawa

Publications and source records attributed to K Sumikawa.

At least 19 recordsLinked to original sources

PubMed1998

Modulation of ACh receptor currents by arachidonic acid.

The present study investigated the effects of arachidonic acid on Torpedo (alpha beta gamma delta) and neuronal nicotinic acetylcholine (ACh) receptors (chick alpha7; rat alpha7, alpha3 beta2, alpha3 beta4, alpha4 beta2, and alpha4 beta4). Arachidonic acid (10 microM) depressed currents through normal Torpedo ACh receptors during treatment and afterward, persistently (>/=30 min) potentiated the currents. The potentiation was blocked by the selective protein kinase C (PKC) inhibitor, GF109203X or PKC inhibitor peptide (PKCI). The depression was not inhibited by any protein kinase inhibitor examined here, but greater in Ca2+-free extracellular solution. Arachidonic acid also potentiated currents through mutant Torpedo ACh receptors lacking PKC phosphorylation sites at Ser333 on the alpha subunit and Ser377 on the delta subunit without depression, but otherwise, it depressed currents through mutant receptors replacing of each Ser by negatively charged amino acid residue, possibly that mimics PKC phosphorylation of the receptors. These results suggest that the depression was due to the direct blocking effect on Ca2+-modulatory sites, which was accelerated under conditions of the receptors phosphorylated by PKC, and that the potentiation was caused by PKC activation, independently of PKC phosphorylation of the receptors. Arachidonic acid reduced currents through chick alpha7 receptors by a mechanism independent of protein kinase activation. In contrast, arachidonic acid potentiated currents through rat alpha7, alpha3 beta2, alpha4 beta2, and alpha4 beta4 receptors, perhaps by the same mechanism as the potentiation observed in Torpedo ACh receptors, although it had no effect on rat alpha3 beta4 receptors. The results of the present study thus demonstrate that arachidonic acid exerts diverse actions on nicotinic ACh receptors by different mechanisms.

Acetylcholine↗

PubMed1998

Function of the rat calcitonin receptors, C1a and C1b, expressed in Xenopus oocytes.

The function of the cloned rat calcitonin receptors, C1a and C1b, was studied in Xenopus oocytes using the two-electrode voltage clamp method. In oocytes expressing the C1a receptors and the cystic fibrosis transmembrane conductance regulator (CFTR), C1a/ CFTR, application (30 sec) of either salmon calcitonin (sCT) or human calcitonin (hCT) activated currents through CFTR. In C1b/CFTR, sCT activated the currents, whereas hCT failed to elicit a response. The sCT induced currents in C1a/CFTR were similar in size to those in C1b/CFTR. Both the activation and the deactivation of sCT-induced currents were slower in C1a/ CFTR. In oocytes expressing C1a or C1b alone, application of relatively high concentrations of sCT induced small oscillatory inward currents. Application of hCT induced small inward currents in C1a alone, but failed to activate currents in C1b alone. These results demonstrate new insights into the signal transduction of calcitonin receptors.

Adenylyl Cyclases↗

PubMed1998

Structural factors contributing to insecticidal and selective actions of neonicotinoids.

Nicotinoids and neonicotinoids are characterized by the presence of the 3-pyridylmethylamine moiety in their structure. In the former, the amino nitrogen atom is ionized, while in the latter the corresponding nitrogen atom is not ionized but bears a partial positive charge. Both types of insecticides interact with nicotinic acetylcholine receptor (nAChR) of insect origin. The poor interaction of neonicotinoids with vertebrate nAChR was shown by its poor binding affinity to the nAChR from Torpedo electric organ and rat brain and poor activation with nAChR expressed in Xenopus oocytes. The full positive charge was essential to interact with the vertebrate nAChR, while the 3-pyridylmethylamine moiety with a partial positive charge was enough to interact with the insect nAChR. For penetration into the insect central nervous system, hydrophobicity seemed to play an important role, as indicated by the binding of the injected compounds to the housefly head nAChR. The ionization reduced hydrophobicity and limited the penetration of nicotinoids, resulting in less insecticidal activity. Among neonicotinoids, nitromethylene type compounds, though far higher in binding affinity, were less hydrophobic than the corresponding nitroimine type, and the net result was better or inferior insecticidal activity. A chlorine atom at the 6 position of the 3-pyridyl group found in commercialized neonicotinoids contributes to increased binding affinity and more importantly hydrophobicity, thus increasing insecticidal activity. N-Me-imidacloprid was found to be a propesticide of imidacloprid.

Animals↗

PubMed1998

Effect of controlled hypotension combined with hemodilution on gastric intramural pH.

STUDY OBJECTIVE: To evaluate the effect of controlled hypotension combined with hemodilution on gastric intramural pH in the clinical setting. DESIGN: Randomized, prospective study. SETTING: Inpatient surgery at Nagasaki Rosai Hospital. PATIENTS: 30 ASA physical status I and II patients scheduled for total hip arthroplasty. INTERVENTIONS: Patients were randomly divided into two groups. Group A (n = 15) received controlled hypotension with mild hemodilution. Group B (n = 15) received controlled hypotension with moderate hemodilution. Hemodilution was carried out after induction of anesthesia. Drawn blood was replaced with 6% hydroxyethyl starch solution. Final hematocrit values were 32 +/- 2% (mean +/- SD) in Group A and 23 +/- 2% in Group B. Controlled hypotension was induced with prostaglandin E1 (PGE1) to maintain mean arterial blood pressure at 55 mmHg for 80 minutes. MEASUREMENTS AND MAIN RESULTS: Measurements included gastric intramural pH (pHi), arterial blood pH (pHa), and plasma lactate. These indices were measured before hemodilution, after hemodilution, 80 minutes after starting hypotension, 60 minutes after recovery from hypotension, and on the first postoperative day. The value of pHi was measured by tonometry. The pHa and lactate values showed no change in either Group A or Group B throughout the time course. Gastric pHi values showed no change in Group A throughout the time course. The pHi value in Group B showed a significant decrease from 7.420 +/- 0.028 to 7.339 +/- 0.034 (p < 0.05) after hemodilution, while it showed no further decrease at 80 minutes after starting hypotension (7.331 +/- 0.039) and 60 minutes after recovery from hypotension (7.330 +/- 0.048). CONCLUSION: The results suggest that moderate hemodilution, such as 23% of hematocrit value, might impair oxygenation in gastrointestinal mucosa, whereas controlled hypotension induced by PGE1 combined with the hemodilution would not increase this impairment.

Aged↗

PubMed1998

Symptoms of spinal stenosis do not improve after epidural steroid injection.

OBJECTIVE: This study was carried out to evaluate the therapeutic effect of epidural steroid injection on pseudoclaudication in patients with lumbar degenerative spinal canal stenosis. DESIGN: Fifty-three patients who complained of pseudoclaudication of less than 20 m in walking distance were randomly divided into three groups. Group 1 (n = 16) underwent epidural injection with 8 ml of saline. Group 2 (n = 18) underwent epidural block with 8 ml of 1% mepivacaine. Group 3 (n = 19) underwent epidural block with a combination of 8 ml of 1% mepivacaine and 40 mg of methylprednisolone. The criteria of evaluation were as follows: excellent effect, > 100 m in walking distance; good effect, 20-100 m in walking distance; poor effect, <20 m in walking distance. RESULTS: In group 1, the numbers of patients who showed a good effect were two (12.5%) after 1 week, one (6.5%) after 1 month, and one (6.5%) after 3 months. In group 2, the numbers of patients who showed a good or excellent result were 10 (55.5%) after 1 week, three (16.7%) after 1 month, and one (5.6%) after 3 months. In group 3, the numbers of patients who showed a good or excellent result were 12 (63.2%) after 1 week, three (15.8%) after 1 month, and one (5.3%) after 3 months. There was no significant difference in the effectiveness of treatment between group 2 and group 3 throughout the time course. CONCLUSION: The results suggest that epidural steroid injection has no beneficial effect on the pseudoclaudication associated with spinal canal stenosis as compared with epidural block with a local anesthetic alone.

Aged↗

PubMed1998

Nefiracetam modulates acetylcholine receptor currents via two different signal transduction pathways.

Nootropic agents are proposed to serve as cognition enhancers. The underlying mechanism, however, is largely unknown. The present study was conducted to assess the intracellular signal transduction pathways mediated by the nootropic nefiracetam in the native and mutant Torpedo californica nicotinic acetylcholine (ACh) receptors expressed in Xenopus laevis oocytes. Nefiracetam induced a short-term depression of ACh-evoked currents at submicromolar concentrations (0.01-0.1 microM) and a long-term enhancement of the currents at micromolar concentrations (1-10 microM). The depression was caused by activation of pertussis toxin-sensitive, G protein-regulated, cAMP-dependent protein kinase (PKA) with subsequent phosphorylation of the ACh receptors; in contrast, the enhancement was caused by activation of Ca(2+)-dependent protein kinase C (PKC) and the ensuing PKC phosphorylation of the receptors. Therefore, nefiracetam interacts with PKA and PKC pathways, which may explain a cellular mechanism for the action of cognition-enhancing agents.

Animals↗

PubMed1997

Lysophosphatidic acid potentiates ACh receptor currents by G-protein-mediated activation of protein kinase C.

The effect of lysophosphatidic acid (lysoPA) on acetylcholine (ACh)-evoked currents was examined using normal and mutant Torpedo nicotinic ACh receptors expressed in Xenopus oocytes. LysoPA enhanced ACh-evoked currents in a washing time- and dose-dependent manner at concentrations of 0.1-3 microM, reaching a maximum of 210% 30 min after treatment, and instead, higher concentrations of lysoPA potentiated to a lesser extent or inhibited the currents. Dose-response curve to ACh was not affected by treatment with lysoPA. Current potentiation by lysoPA was fully inhibited by a broad G-protein inhibitor, guanosine-5'-O-(2-thiodiphosphate) (GDPbetaS), but not by a Gi/o-protein inhibitor, pertussis toxin (PTX). Additionally, the selective protein kinase C (PKC) inhibitor, GF109203X, blocked the potentiation, although the effect of lysoPA was not affected by the selective cAMP-dependent protein kinase (PKA) inhibitor, H-89, or mitogen-activated protein kinase inhibitor, PD98059. LysoPA (3 microM) enhanced currents to 130% in Ca2+-free extracellular solution, and to 150% still in the mutant ACh receptors lacking PKC phosphorylation sites. The potentiation was also completely blocked by GF109203X. These results indicate that lysoPA potentiates ACh receptor currents by PTX-insensitive G-protein-mediated activation of Ca2+-dependent/-independent PKCs with subsequent phosphorylation of the receptors and by an unknown factor or process activated by PKC activation.

Animals↗

PubMed1997

A serum factor potentiates ACh and AMPA receptor currents via differential signal transduction pathways.

A serum factor is recognized to interact with a protein kinase C (PKC) pathway. Indeed, treatment with fetal bovine serum enhanced ACh-evoked currents by PKC activation in the neuronal nicotinic ACh receptors (alpha7) and Torpedo ACh receptors expressed in Xenopus oocytes. In addition, potentiation of ACh-evoked currents induced by fetal bovine serum was observed also in the mutant Torpedo ACh receptors lacking potent PKC phosphorylation sites at Ser333 on the alpha subunit and Ser377 on the delta subunit; the potentiation was inhibited by the PKC inhibitor, PKC inhibitor peptide (PKCI), indicating that ACh receptor currents were enhanced by PKC activation but not by PKC phosphorylation of the receptors. On the other hand, fetal bovine serum enhanced kainate-evoked currents in oocytes expressing the alpha-amino3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, GluR1,3. The enhancement was not affected by the PKC inhibitors, PKCI or GF109203X, and instead, was inhibited by the Ca2+/calmodulin-dependent kinase II (CaMKII) inhibitor, KN-62. These results suggest that serum is not only involved in PKC activation but in CaMKII activation, and that thereby ACh receptor currents and AMPA receptor currents are each potentiated.

Animals↗

PubMed1997

Short-term depression and long-term enhancement of ACh-gated channel currents induced by linoleic and linolenic acid.

The effects of cis-unsaturated free fatty acids such as linoleic and linolenic acid on ACh-evoked currents were examined using normal and mutant nicotinic acetylcholine (ACh) receptors lacking protein kinase C (PKC) phosphorylation sites on the alpha and delta subunits expressed in Xenopus oocytes. These free fatty acids reduced ACh-gated channel currents during treatment and to a greater extent in Ca2+-free extracellular solution. After treatment, the currents were enhanced as the drug was washed out, but this effect was not observed in the absence of extracellular Ca2+. Linolenic acid was more potent of the current enhancement (300% of the control) than linoleic acid (190% of the control). The current enhancement induced by these free fatty acids was inhibited by the selective PKC inhibitor, GF109203X, while the current depression was not affected. Furthermore, these lipids decreased ACh-evoked currents in mutant ACh receptors to the same extent as in normal ACh receptors, but never enhanced the currents. These results indicate that linoleic and linolenic acid have biphasic actions on ACh receptor currents; a short-term depression and a long-term enhancement. The short-term depression may be due to an interaction with the ACh receptor channels, presumably at Ca2+ binding sites. The long-lasting enhancement appears to result from Ca2+-dependent PKC activation followed by PKC phosphorylation of the ACh receptors.

Acetylcholine↗

PubMed1997

Oleic acid enhances ACh receptor currents by activation of Ca2+/calmodulin-dependent protein kinase II.

Oleic acid, a cis-unsaturated free fatty acid, is proposed to be involved in the protein kinase C (PKC) activation pathway. Its biological actions, however, have not been well-characterized. We examined the effects of oleic acid on acetylcholine (ACh)-gated channel currents using Torpedo nicotinic ACh receptors expressed in Xenopus oocytes. Oleic acid (10 microM) enhanced the currents, reaching a maximum (140%) 20 min after treatment, while no enhancement was observed in Ca(2+)-free extracellular solution. The current potentiation by oleic acid was not inhibited by PKC inhibitors such as PKCI or GF109203X. Furthermore, oleic acid potentiated the currents in mutant ACh receptors lacking potential PKC phosphorylation sites. In contrast, the potentiation was fully inhibited by a CaMKII inhibitor, KN-62. These results strongly suggest that oleic acid potentiates ACh receptor currents by activation of calmodulin-dependent protein kinase II (CaMKII), independent of the PKC pathway.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

PubMed1997

Adenovirus-mediated NMDA receptor knockouts in the rat hippocampal CA1 region.

Adenoviral antisense constructs of the rat N-methyl-D-aspartate (NMDA) receptor subunit 1 (R1) were assessed for creating NMDAR1 knockouts in rat hippocampal CA1 regions in vivo. In situ hybridization analyses showed that virus-derived antisense transcripts were detected up to 5 weeks postinfection (p.i.). Although immunological methods failed to demonstrate a reduction of NMDA receptor protein, whole-cell recording showed that neurons in the transduced regions were deficient in NMDA receptor-mediated synaptic currents, but not alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptor (AMPAR)-mediated synaptic currents. Thus, the data suggest that adenovirus technology can be used to locally knockout specific gene function for dissecting molecular mechanisms of synaptic plasticity.

2-Amino-5-phosphonovalerate↗

PubMed1997

N-glycosylation at the conserved sites ensures the expression of properly folded functional ACh receptors.

The role of the conserved carbohydrate moiety in the expression of complete acetylcholine receptor (AChR), alpha2 beta gamma delta was re-investigated by expressing additional site-directed mutant subunits, lacking an N-glycosylation site, in Xenopus oocytes. All mutant subunits were stably expressed and appeared to associate with other normal subunits; however, removal of carbohydrate on the alpha subunit inhibited the formation of 125I-alpha-bungarotoxin (alpha-BuTX) binding sites and functional ACh-gated ion channels. 125I-alpha-BuTX binding to AChRs was also significantly reduced by removal of the conserved carbohydrate on the gamma or delta subunits. Immunoprecipitation with monoclonal antibodies that recognize the two distinct alpha-BuTX sites on the AChR indicated that the mutant gamma subunit did not interfere with efficient formation of the alpha-BuTX binding site at the alpha/delta interface, but loss of the carbohydrate did interfere with formation of the alpha-BuTX binding site at the alpha/mutant gamma interface. A similar result was obtained with the mutant delta subunit. Furthermore, the mutant gamma and mutant delta subunits were not incorporated efficiently into the mature (correct tertiary conformation capable of alpha-BuTX binding) alpha beta delta or alpha beta gamma complexes, respectively. Since both mutant gamma and mutant delta subunits were capable of assembling with the alpha subunits (immature assembly), these results suggest that the formation of the two alpha-BuTX binding sites requires correct folding of the alpha gamma and alpha delta complexes, which is aided by the conserved carbohydrate on the gamma and delta subunits. Electrophysiological experiments demonstrated that functional receptors containing mutant subunits were produced, but the functional properties of the mutant receptors were differentially altered, depending on the subunit mutated. Together, our results suggest that N-glycosylation of AChR subunits ensures the correct folding of important functional domains and expression of proper functional receptors in the plasma membrane.

Acetylcholine↗

PubMed1997

Long-lasting enhancement of ACh receptor currents by lysophospholipids.

Lysophosphatidylcholine (LysoPtdCho) and lysophosphatidylethanolamine (LysoPtdEtn), which are formed by phospholipase A2-catalyzed hydrolysis of phosphatidylcholine (PtdCho) and phosphatidylethanolamine (PtdEtn), respectively, are proposed to be involved in protein kinase C (PKC) activation. Their physiological significance, however, remains unclear. We examined the effects of lysoPtdCho and lysoPtdEtn on acetylcholine (ACh) receptor currents using oocytes expressing Torpedo nicotinic ACh receptors. LysoPtdCho enhanced the currents in a washing time- and dose-dependent manner (10 nM-1 microM), reaching a maximum of 191% at 20 min after treatment. The currents were enhanced to a lesser extent at higher concentrations, and instead, inhibited to 81% at 10 microM. Likewise, lysoPtdEtn also potentiated the currents to 200% at 10 microM, although its dose-dependent curve shifted to right as compared with that of lysoPtdCho. The current potentiation was blocked by a PKC inhibitor, PKC inhibitor peptide (PKCI), or removal of extracellular Ca2+. In addition, lysoPtdCho and lysoPtdEtn enhanced the currents in mutant ACh receptors lacking PKC phosphorylation sites on the alpha and delta subunits. These results suggest that lysophospholipids such as lysoPtdCho and lysoPtdEtn potentiated ACh receptor currents by Ca2+-dependent PKC activation, but that this effect did not require PKC phosphorylation of the ACh receptor.

Acetylcholine↗

PubMed1997

Catecholamine and renin-angiotensin response during controlled hypotension induced by prostaglandin E1 combined with hemodilution during isoflurane anesthesia.

STUDY OBJECTIVE: To evaluate the catecholamine and renin-angiotensin response during controlled hypotension combined with hemodilution in the clinical setting. DESIGN: Randomized, prospective study. SETTING: Inpatient surgery at Nagasaki Rosai Hospital. PATIENTS: 30 ASA physical status I and II female patients scheduled for total hip arthroplasty. INTERVENTIONS: Patients were randomly divided into three groups. Group A (N = 10) received hemodilution alone. Group B (N = 10) received controlled hypotension alone. Group C (N = 10) received hemodilution plus controlled hypotension. Hemodilution was carried out after induction of anesthesia, in which drawn blood was replaced with 6% hydroxyethyl starch, and the final hematocrit value was approximately 22%. Controlled hypotension was induced with prostaglandin E1 (PGE1) to maintain mean arterial blood pressure at 55 mmHg for 80 minutes. MEASUREMENTS AND MAIN RESULTS: Measurements included plasma renin activity (RA) and plasma concentrations of angiotensin-II (AG-II), aldosterone (AS), norepinephrine (NE), and epinephrine (EP). These indices were measured before hemodilution, after hemodilution, 80 minutes after starting hypotension, and 60 minutes after recovery from hypotension. Hemodilution alone caused no significant change in the values throughout the time course. Controlled hypotension alone caused significant increases in plasma concentrations of NE (+295%) and EP (+203%) at 80 minutes after starting hypotension, whereas it caused no change in plasma RA and plasma concentrations of AG-II and AS. Hemodilution plus controlled hypotension caused significant increases in plasma RA (+271%) and plasma concentrations of AG-II (+188%), AS (+199%), NE (+279%), and EP (+184%) at 80 minutes after starting hypotension. CONCLUSION: The combination of hemodilution and PGE1 induced controlled hypotension causes significant responses, especially in a renin-angiotensin-aldosterone system under isoflurane anesthesia.

Aged↗

PubMed1997

The endothelin ETA receptor exists in the caudal solitary tract nucleus of the rat brain.

1. The receptor autoradiographic method done on the rat lower brain stem and cerebellum plus 125I-endothelin-1, BQ-123, an antagonist for the endothelin ETA receptor, and sarafotoxin S6c, an agonist for the ETB receptor, revealed minute amounts of the ETA receptor coexisting with the ETB receptor in the caudal solitary tract nucleus of the rat lower brain stem. 2. The ETB receptor is present predominantly in other parts of the lower brain stem. 3. Knowledge of the heterogeneous distribution of the central endothelin receptor subtypes aids in understanding the neurophysiology of endothelins.

Amino Acid Sequence↗

PubMed1997

Combined effects of prolonged prostaglandin E1-induced hypotension and haemodilution on human hepatic function.

Combined effects of prolonged prostaglandin E1 (PGE1)-induced hypotension and haemodilution on hepatic function were studied in 30 patients undergoing hip surgery. The patients were randomly allocated to one of three groups; those in group A (n = 10) were subjected to controlled hypotension alone, those in group B (n = 10) to haemodilution alone and those in group C (n = 10) to both controlled hypotension and haemodilution. Haemodilution in groups B and C was produced by withdrawing approximately 1000 mL of blood and replacing it with the same amount of dextran solution, and final haematocrit values were 21 or 22%. Controlled hypotension in groups A and C was induced with PGE1 to maintain mean arterial blood pressure at 55 mmHg for 180 min. Measurements included arterial ketone body ratio (AKBR, aceto-acetate/3-hydroxybutyrate) and clinical hepatic function parameters. AKBR and biological hepatic function tests showed no change throughout the time course in groups A and B. In group C, AKBR showed a significant decrease at 120 min (-40%) and at 180 min (-49%) after the start of hypotension and at 60 min (-32%) after recovery of normotension, and SGOT, SGPT, LDH and total bilirubin showed significant increases after operation. The results suggest that a prolonged combination of more than 120 min of PGE1-induced hypotension and moderate haemodilution would cause impairment of hepatic function.

Adult↗

PubMed1997

Acute haemodilution and prostaglandin E1-induced hypotension: effects on the coagulation-fibrinolysis system.

The effects of acute haemodilution, during prostaglandin E1 (PGE1)-induced hypotension, on the blood coagulation-fibrinolysis system were studied in 40 patients undergoing hip surgery. The patients were randomly divided into four groups of 10 patients each; Group A (control) received no induced hypotension or haemodilution, group B received hypotension alone, group C received haemodilution alone and group D received the combination of induced hypotension and haemodilution. Haemodilution in groups C and D was produced by drawing approximately 1000 mL of blood and replacing it with the same amount of 6% hydroxyethyl starch. Induced hypotension in groups B and D was conducted with PGE1 and mean blood pressure was maintained at 55 mmHg. The mean dosage of PGE1 was 648 micrograms in group B and 661 micrograms in group D. In the control and PGE1-induced hypotension groups there was no significant change in platelet count (PLT), prothrombin time (PT), activated partial thromoplastin time (aPTT), fibrinogen (FIB), antithrombin-III (AT-III) or plasminogen (PLG). Haemodilution alone caused significant decreases in PLT (-43%), PT (+21%), FIB (-33%), AT-III (-21%) and PLG (-27%), and a significant increase in aPTT (+26%), whereas the combination of PGE1-induced hypotension did not cause any further change in these parameters. Serum-fibrin degradation products (FDP) significantly increased (+300%) and PLG significantly decreased (-30%) after surgery in all groups. It can be concluded that acute haemodilution to a haematocrit value of 22 +/- 2% causes a slight coagulopathy, which is not enhanced when combined with PGE1-induced hypotension.

Aged↗

PubMed1997

Effects of intravenous anesthetics on the contraction and response of rat trachea to phosphatidylinositol.

Some intravenous anaesthetics have significant effects on the tonicity of airway smooth muscle. There are evidences for a direct relationship between airway smooth muscle contraction and phosphatidylinositol (PI) response. The aims of this study were to clarify 1) the effects of anaesthetics on the cholinergically induced contraction, and 2) the relationship between the effects on the PI response and the contraction. Rat tracheal rings or slices were incubated in Krebs-Henseleit solution containing 5.5 microM carbachol (CCh) in the presence of varying doses of anaesthetics. Thiamylal, fentanyl, ketamine and midazolam all attenuated the CCh-induced contraction. On the other hand, thiamylal augmented inositol monophosphate (IP1) accumulation, whilst ketamine, midazolam and morphine did not have the effect, and fentanyl significantly attenuated IP1 accumulation. These data suggest that airway smooth muscle can be relaxed by intravenous anaesthetics, and that the relaxing effects are not always dependent on the PI system.

Analysis of Variance↗