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D J Rowbotham

Publications and source records attributed to D J Rowbotham.

At least 19 recordsLinked to original sources
PubMed2002

Effects of remifentanil and alfentanil on the cardiovascular responses to induction of anaesthesia and tracheal intubation in the elderly.

BACKGROUND: We compared the effects of remifentanil and alfentanil on arterial pressure and heart rate at induction of anaesthesia and tracheal intubation in 40 ASA I-III patients aged greater than 65 yr, in a randomized double-blind study. METHODS: Patients received either remifentanil 0.5 microg kg(-1) over 30 s, followed by an infusion of 0.1 microg kg min(-1) (group R) or alfentanil 10 microg kg(-1) over 30 s, followed by an infusion of saline (group A). Anaesthesia was then induced with propofol, rocuronium, and 1% isoflurane with 66% nitrous oxide in oxygen. RESULTS: Systolic arterial pressure (SAP) and mean arterial pressure (MAP) decreased after the induction of anaesthesia (P<0.05) and increased for 3 min after intubation in both groups (P<0.05), but remained below baseline values throughout. Heart rate remained stable after induction of anaesthesia but increased significantly from baseline after intubation for 1 and 4 min in groups R and A, respectively (P<0.05). There were no significant between-group differences in SAP, MAP, and heart rate. Diastolic pressure was significantly higher in group A than group R at 4 and 5 min after intubation (P<0.05). Hypotension (SAP < 100 mm Hg) occurred in four patients in group R and three patients in group A. CONCLUSIONS: Remifentanil and alfentanil similarly attenuate the pressor response to laryngoscopy and intubation, but the incidence of hypotension confirms that both drugs should be used with caution in elderly patients.

Aged↗
PubMed2001

Temperature-dependent activation of recombinant rat vanilloid VR1 receptors expressed in HEK293 cells by capsaicin and anandamide.

Capsaicin activates vanilloid (VR1) receptors found on sensory neurons. These ligand-gated ion channels are also sensitive to low pH, elevated temperature and the endocannabinoid, anandamide. In this study, we have measured capsaicin- and anandamide-induced elevations in intracellular calcium concentrations ([Ca(2+)](i)) in fura-2 loaded HEK293 cells stably expressing the rat VR1 receptor at 22, 37 and 50 degrees C. Both capsaicin and anandamide produced a concentration-dependent elevation in [Ca(2+)](i) at all temperatures. pEC(50) values were 7.74 and 5.69 at 22 degrees C and 6.90 and 5.15 at 37 degrees C for capsaicin and anandamide, respectively. At 50 degrees C, the pEC(50) value for capsaicin was 6.36 but the response to anandamide did not saturate. Responses to both agonists were sensitive to ruthenium red and capsazepine at all temperatures. This temperature-dependent reduction in potency may result from desensitization.

Animals↗
PubMed2001

Interaction of local anaesthetic agents with the endogenous norepinephrine transporter in SH-SY5Y human neuroblastoma cells.

Use of intravenous guanethidine for the treatment of complex regional pain syndrome type I is of variable efficacy. Guanethidine injection is painful, so local anaesthetic is co-administered. We hypothesize that local anaesthetic inhibits uptake of guanethidine and hence reduces its efficacy. In this study we have examined the effects of a range of local anaesthetic agents on the uptake of [3H]norepinephrine ([3H]NE) (as a surrogate for guanethidine) and the binding of [3H]nisoxetine to the NE transporter in cultured SH-SY5Y human neuroblastoma cells. All local anaesthetic agents inhibited NE uptake with a rank order cocaine>tetracaine>procaine(esters), dibucaine > bupivacaine > prilocaine > lidocaine (amides). In addition all anaesthetic agents displaced [3H]nisoxetine with a rank order cocaine > tetracaine > dibucaine > procaine > prilocaine > bupivacaine > lidocaine. There was a positive correlation between [3H]NE uptake and [3H]nisoxetine binding. Our data suggest that when local anaesthetic and guanethidine are co-administered the former may reduce uptake of the latter and hence reduce the clinical efficacy of guanethidine.

Anesthetics, Local↗
PubMed2001

Characterisation and comparison of novel ligands for the nociceptin/orphanin FQ receptor.

Studies of nociceptin/orphanin FQ (NC) have been hampered by the paucity of available ligands with activity at the nociceptin receptor (NCR). In this study we have compared the agonist profile of NC and a novel NCR agonist, Ro65-6570, in a series of radioligand binding studies and effects on forskolin-stimulated cAMP formation in Chinese hamster ovary (CHO) cells expressing the recombinant human NCR (CHOhNCR). In addition, we report the effects of three antagonists, [Nphe1]NC(1-13)NH2, J-113397 and III-BTD, on these responses. In radioligand binding studies Ro65-6570, [Nphe1]NC(1-13)NH2, J-113397 and III-BTD displaced [3H]NC with similar pKi values (8.4-8.8). This compares with a pK(D) of 10.2 for NC in a direct saturation experiment. [Nphe1]NC(1-13)NH2 and J-113397 showed at least 100-fold selectivity over classical opioid receptors. Both NC and Ro65-6570 produced a concentration-dependent inhibition of cAMP formation with pEC50 values of 9.56+/-0.06 and 8.68+/-0.04, respectively. Maximum inhibition achieved was 100%. [Nphe1]NC(1-13)NH2, J-113397 and III-BTD produced a parallel rightward shift in the concentration-response curves to both NC and Ro65-6570 with pK(B) values of approximately 6.5, approximately 7.5 and approximately 7.7, respectively. Importantly, all three antagonists were devoid of residual agonist activity. Collectively, these data indicate the value of Ro65-6570, [Nphe1]NC(1-13)NH2, J-113397 and III-BTD in studies of the physiological role played by NC. However, due to the relatively poor selectivity of Ro65-6570 and III-BTD caution should be exercised when using tissues that co-express micro-opioid receptors.

Animals↗
PubMed2001

Effects of nociceptin and endomorphin 1 on the electrically stimulated human vas deferens.

AIMS: To examine the effects of nociceptin (NC) and endomorphin 1 (EM1) on electrical field stimulation (EFS)-induced contractions of the human vas deferens (hVD). METHODS: Concentration-response curves to NC and EM1 were constructed in the absence and in presence of peptidase inhibitors (PI). In some experiments a NC receptor antagonist, [Phe1psi(CH2-NH)Gly2]NC(1-13)NH2 [F/G], 10 microM) or naloxone (1 microM) were included. RESULTS: All data are mean(95%CI). In the presence of PI, NC inhibited twitches (Emax = 67(44,90)%; pEC50 = 7.28(6.95,7.61)). NC inhibition was sensitive to [F/G]. EM1 also inhibited twitches both in the absence (Emax = 82(73,91)% pEC50 = 7.07(6.92,7.22)) and presence (Emax = 83(76,90)%; pEC50 = 7.00(6.91, 7.09)) of PI. EM1 inhibition was sensitive to naloxone. CONCLUSIONS: These data suggest that hVD express NC and opioid receptors that inhibit neurogenic contractions.

Analgesics, Opioid↗
PubMed2001

Comparison of effects of remifentanil and alfentanil on cardiovascular response to tracheal intubation in hypertensive patients.

In a randomized double-blind study, we compared the effect of remifentanil and alfentanil on the cardiovascular response to laryngoscopy and tracheal intubation in patients on long-term treatment for hypertension. Forty ASA II-III patients were allocated to receive (i) remifentanil 0.5 microg kg(-1) followed by an infusion of 0.1 microg kg min(-1) or (ii) alfentanil 10 microg kg(-1) followed by an infusion of saline; all patients received glycopyrrolate 200 microg before the study drug. Anaesthesia was induced with propofol and rocuronium and maintained with 1% isoflurane and 66% nitrous oxide in oxygen. Laryngoscopy and tracheal intubation were performed after establishment of neuromuscular block. Arterial pressure and heart rate (HR) were measured non-invasively at 1 min intervals from 3 min before induction until 5 min after intubation. Systolic (SAP), diastolic and mean arterial pressure decreased significantly after induction in both groups (P<0.05). Maximum increases in mean SAP after laryngoscopy and intubation were 35 and 41 mm Hg in the remifentanil and alfentanil groups, respectively. After intubation, arterial pressure did not increase above baseline values in either group. HR remained stable after induction of anaesthesia, but increased above baseline values after intubation. Mean maximum HR was 87 beats min(-1) for the remifentanil group (12 beats min(-1) above baseline; P=0.065) and 89 beats min(-1) for the alfentanil group (15 beats min(-1) above baseline; P<0.05). There were no significant differences between groups in HR or arterial pressure at any time. There were no incidences of bradycardia. Seven patients in the remifentanil group and four in the alfentanil group received ephedrine for hypotension (i.e. SAP<100 mm Hg).

Adult↗
PubMed2001

Advances in pain.

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Acute Disease↗
PubMed2000

Endomorphin-1 induced desensitization and down-regulation of the recombinant mu-opioid receptor.

1. Endomorphin-1 (E1) is a peptide with high affinity and selectivity for the mu-opioid receptor. The aim of this study was to determine if endomorphin-1 caused desensitization and down-regulation of the mu-opioid receptor expressed in Chinese hamster ovary cells. 2. Following 10 microM E1 pre-treatment, desensitization was assessed by measuring cyclic AMP inhibition, down-regulation was assessed by [(3)H]-diprenorphine ([(3)H]-DPN) binding and immuno-blotting. 3. Pre-treatment of CHO mu cells with 10 microM E1 for 11 and 18 h caused significant reduction in cyclic AMP inhibition. (11 h=39.0+/-16.7%, 18 h 47.0+/-11.1% reduction). 4. At 18 h E1 pre-treatment there was an enhancement (4.5 fold) of cyclic AMP production under forskolin stimulated conditions accompanied by a small rightward shift in the concentration-response curve (pEC(50) control=7.8+/-0.3, pEC(50) E1=7.3+/-0.2) when cells were re-challenged with E1. 5. In membranes prepared from untreated and 0.5 h E1 pre-treated cells, addition of GTP gamma S produced a significant rightward shift in the concentration response curves for E1 displacement of [(3)H]-DPN (0 h K(i) control=7.86+/-0.11, GTP gamma S=7.37+/-0.15; 0.5 h K(i) control=7.92+/-0.12, GTP gamma S=7.36+/-0.08) This was not observed in membranes prepared from cells that had been treated with E1 for 18 h (18 h K(i) control=7.69+/-0. 11, GTP gamma S=7.75+/-0.08). 6. In whole cells E1 treatment caused a rapid loss of cell surface receptors such that at 0.5 h there was a 30.5+/-1.5 reduction (this was unchanged for 18 h). In crude membranes a loss of receptors was also observed using radioligand binding or immuno-blotting protocols. 7. These data show that E1 causes desensitization and down-regulation of the rat mu-opioid receptor expressed in CHO cells. However, these two responses appear temporally distinct.

Animals↗
PubMed2000

Comparison of different doses of remifentanil on the cardiovascular response to laryngoscopy and tracheal intubation.

We have compared three bolus and infusion regimens of remifentanil on the cardiovascular response to laryngoscopy and orotracheal intubation in three groups of 20 ASA I-II female patients, in a randomized, double-blind study. Patients in group 1 received glycopyrolate 200 micrograms i.v. followed by a bolus dose of remifentanil 1 microgram kg-1 over 30 s and an infusion of remifentanil at a rate of 0.5 microgram kg-1 min-1. The other patients received remifentanil 0.5 microgram kg-1 over 30 s and an infusion of 0.25 microgram kg-1 min-1 with (group 2) or without (group 3) pretreatment with glycopyrrolate 200 micrograms. All patients then received a sleep dose of propofol, rocuronium 0.6 mg kg-1 and 1% isoflurane with 67% nitrous oxide in oxygen. Laryngoscopy and tracheal intubation were performed 3 min later. Heart rate and arterial pressure were recorded at 1-min intervals from before induction of anaesthesia until 5 min after intubation. Baseline heart rate was similar in all groups, but decreased in group 3 (no glycopyrrolate) after induction and remained significantly lower after intubation compared with the other groups (P < 0.05). Heart rate and arterial pressure increased slightly after intubation in each group but there were no significant differences in mean arterial pressure between groups at any time. The incidence of bradycardia (one patient in group 2) and hypotension (two patients in groups 1 and 2 and three patients in group 3) was low.

Adult↗
PubMed2000

Warm air sensation for assessment of block after spinal anaesthesia.

We have evaluated a new method of assessing dermatomal sensory levels after regional anaesthesia based on warm sensation. Sensory levels were assessed in 30 patients after spinal anaesthesia using a respiratory gas humidifier, adapted to deliver a constant flow of warm air at 40 +/- 0.2 degrees C. This was compared with the cold sensation from ethyl chloride spray. The frequency distribution of the dermatomal differences showed 96.6% of the comparisons were between +1 and -1 dermatomes. The median difference in dermatomal levels between the two methods of assessment was 0 (interquartile range 0-1) (P = 0.65). We conclude that the warm air method compares favourably with ethyl chloride spray and both can be used interchangeably.

Adolescent↗
PubMed2000

Effects of intravenous anesthetic agents on glutamate release: a role for GABAA receptor-mediated inhibition.

BACKGROUND: Many anesthetic agents are known to enhance the alpha1beta2gamma2S gamma-aminobutyric acid type A (GABAA) chloride current; however, they also depress excitatory neurotransmission. The authors evaluated two hypotheses: intravenous anesthetic agents inhibit glutamate release and any observed inhibition may be secondary to GABAA receptor activation. METHODS: Cerebrocortical slices were prepared from Wistar rats. After perfusion in oxygenated Krebs buffer for 60 min at 37 degrees C, samples for glutamate assay were obtained at 2-nmin intervals. After 6 min, a 2-min pulse of 46 mM K+ was applied to the slices (S1); this was repeated after 30 min (S2). Bicuculline (1-100 microM) was applied when the S1 response returned to basal level, and 10 min later, thiopental (1-300 micro/M), propofol (10 microM), or ketamine (30 microM) were also applied until the end of S2. Perfusate glutamate concentrations were measured fluorometrically, and the area under the glutamate release curves was expressed as a ratio (S2/S1). RESULTS: Potassium (46 mM) evoked a monophasic release of glutamate during S1 and S2, with a mean control S2/S1 ratio of 1.07 +/- 0.33 (mean +/- SD, n = 96). Ketamine and thiopental produced a concentration-dependent inhibition of K+-evoked glutamate release with half-maximum inhibition of release values of 18.2 and 10.9 /microM, respectively. Release was also inhibited by propofol. Bicuculline produced a concentration dependent reversal of thiopental inhibition of glutamate release with a half-maximum reversal of the agonist effect of 10.3 microM. Bicuculline also reversed the effects of propofol but not those of ketamine. CONCLUSIONS: The authors' data indicate that thiopental, propofol, and ketamine inhibit K+-evoked glutamate release from rat cerebrocortical slices. The inhibition produced by thiopental and propofol is mediated by activation of GABAA receptors, revealing a subtle interplay between GABA-releasing (GABAergic) and glutamatergic transmission in anesthetic action.

Anesthetics, Intravenous↗
PubMed1999

Anaesthesia.

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Anesthesia↗
PubMed1999

The effect of C-terminal truncation of the recombinant delta-opioid receptor on Ca2+i signaling.

We have previously shown a stimulatory coupling of the recombinant delta-opioid receptor to phospholipase C leading to production of inositol (1,4,5) triphosphate [Ins(1,4,5)P3] that is affected by truncation of the C-terminus of the receptor. Using a C-terminal mutant of the delta-opioid receptor lacking the final 37 amino acids (CHOdelta37), we examined its coupling to intracellular calcium ion concentration ([Ca2+]i) compared to the full length wild type receptor (CHOdeltaWT) in transfected Chinese hamster ovary (CHO) cells. D-[Pen2,5]enkephalin (DPDPE) mediated increases in [Ca2+]i were measured fluorimetrically in fura-2 loaded whole cell suspensions. DPDPE produced time- and concentration-dependent increases in [Ca2+]i in CHOdeltaWT and CHOdelta37. In both cell types the DPDPE simulated increase in [Ca2+]i was naloxone reversible and pertussis toxin and thapsigargin sensitive. Removal of the C-terminus resulted in a rightward shift of the Ca2+ release concentration-response curve [pEC50 = 8.43 +/- 0.13 and 6.08 +/- 0.25 for CHOdeltaWT and CHOdelta37, respectively]. These data indicate that the C-terminus of the recombinant delta-opioid receptor is important in [Ca2+]i coupling and may be attributed to the effect of C-terminus truncation on phospholipase C coupling reported previously.

Amino Acid Sequence↗
PubMed1999

Comparison of the effects of [Phe1psi(CH2-NH)Gly2]nociceptin(1-13)NH2 in rat brain, rat vas deferens and CHO cells expressing recombinant human nociceptin receptors.

Nociceptin(NC) is the endogenous ligand for the opioid receptor like-1 receptor (NC-receptor). [Phe1(psi)(CH2-NH)Gly2]Nociceptin(1-13)NH2 ([F/G]NC(1-13)NH2) has been reported to antagonize NC actions in peripheral guinea-pig and mouse tissues. In this study, we investigated the effects of a range of NC C-terminal truncated fragments and [F/G]NC(1-13)NH2 on NC receptor binding, glutamate release from rat cerebrocortical slices (rCX), inhibition of cyclic AMP accumulation in CHO cells expressing the NC receptor (CHO(NCR)) and electrically evoked contractions of the rat vas deferens (rVD). In radioligand binding assays, a range of ligands inhibited [125I]-Tyr14-NC binding in membranes from rCX and CHO(NCR) cells. As the peptide was truncated there was a general decline in pKi. [F/G]NC(1-13)NH2 was as potent as NC(1-13)NH2. The order of potency for NC fragments to inhibit cyclic AMP accumulation in whole CHO(NCR) cells was NCNH2> or =NC=NC(1-13)NH2>NC(1-12)NH2> >NC(1-11)NH2. [F/G]NC(1-13)NH2 was a full agonist with a pEC50 value of 8.65. NCNH2 and [F/G]NC(1-13)NH2 both inhibited K+ evoked glutamate release from rCX with pEC50 and maximum inhibition of 8.16, 48.5+/-4.9% and 7.39, 58.9+/-6.8% respectively. In rVD NC inhibited electrically evoked contractions with a pEC50 of 6.63. Although [F/G]NC(1-13)NH2, displayed a small (instrinsic activity alpha = 0.19) but consistent residual agonist activity, it acted as a competitive antagonist (pA2 6.76) in the rVD. The differences between [F/G]NC(1-13)NH2 action on central and peripheral NC signalling could be explained if [F/G]NC(1-13)NH2 was a partial agonist with high strength of coupling in the CNS and low in the periphery. An alternative explanation could be the existence of central and peripheral receptor isoforms.

Animals↗
PubMed1999

The effects of endomorphin-1 and endomorphin-2 in CHO cells expressing recombinant mu-opioid receptors and SH-SY5Y cells.

1 Endomorphin-1 and -2 (E-1/E-2) have been proposed as endogenous ligands for the mu-opioid receptor. The aims of this study are to characterize the binding of E-1/E-2 and the subsequent effects on cyclic AMP formation and [Ca2+]i levels in SH-SY5Y and Chinese hamster ovary (CHO) cells expressing endogenous and recombinant mu-opioid receptors. 2 E-1 displaced [3H]-diprenorphine ([3H]-DPN) binding in CHO micro and SH-SY5Y membranes with pKi values of 8.02+/-0.09 and 8.54+/-0.13 respectively. E-2 displaced [3H]-DPN binding in CHOmu and SH-SY5Y cells with pKi values of 7.82+/-0.11 and 8.43+/-0.13 respectively. E-1/E-2 bound weakly to CHOdelta and CHOkappa membranes, with IC50 values of greater than 10 microM. 3 In CHOmu cells, E-1/E-2 inhibited forskolin (1 microM) stimulated cyclic AMP formation with pIC50 values of 8.03+/-0.16 (Imax = 53.0+/-9. 3%) and 8.15+/-0.24 (Imax = 56.3+/-3.8%) respectively. In SH-SY5Y cells E1/E2 inhibited forskolin stimulated cyclic AMP formation with pIC50 values of 7.72+/-0.13 (Imax=46.9+/-5.6%) and 8.11+/-0.31 (Imax = 40.2+/-2.8%) respectively. 4 E-1/E-2 (1 microM) increased [Ca2+]i in fura-2 loaded CHOmu cell suspensions in a thapsigargin sensitive and naloxone reversible manner. Mean increases observed were 106+/-28 and 69+/-6.7 nM respectively. In single adherent cells E-1/E-2 (1 microM) increased [Ca2+]i with a mean 340/380 ratio change of 0.81+/-0.09 and 0.40+/-0.08 ratio units respectively. E-1/E-2 failed to increase intracellular calcium in CHOdelta, CHOkappa and SH-SY5Y cells. 5 These data show that E-1/E-2 bind with high affinity and selectivity to mu-opioid receptors and modulate signal transduction pathways typical of opioids. This provides further evidence that these two peptides may be endogenous ligands at the mu-opioid receptor.

Analgesics, Opioid↗
PubMed1999

Piritramide.

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Analgesics, Opioid↗