| Do local anaesthetics interact with dihydropyridine binding sites on neuronal L-type Ca2+ channels? | |
| | |
MedLine Citation:
|
PMID: 9068339 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
We have examined the interaction of procaine, prilocaine, lignocaine, bupivacaine, amylocaine and R(+) and S(-) ropivacaine with L-type voltage-sensitive Ca2+ channels in rat cerebrocortical membranes. Membranes were prepared in Tris HCl 50 mmol litre-1, pH 7.4, by homogenization and centrifugation. Binding assays were performed in 1-ml volumes of Tris HCl 50 mmol litre-1, pH 7.4, for 90 min at room temperature using approximately 200 micrograms of protein. Non-specific binding was defined in the presence of nifedipine 10(-5) mol litre-1, and bound and free radioactivity were separated by vacuum filtration. The effects of local anaesthetics were determined by displacement of [3H]PN200-110 (approximately 0.2 nmol litre-1), a radiolabelled 1,4- dihydropyridine (DHP) L-channel antagonist. The concentration of displacer producing 50% displacement was corrected for the competing mass of [3H]PN200-110 to yield the affinity constant, K50. All local anaesthetics displaced [3H]PN200-110 in a dose-dependent manner with a rank order potency of (K50, mmol litre-1) bupivacaine (0.48), amylocaine (0.74), lignocaine (1.09), prilocaine (2.06) and procaine (2.09). Ropivacaine enantiomers did not show stereo-selective displacement, with K50 values of 0.99 and 0.92 mmol litre-1 for R(+) and S(-) ropivacaine, respectively. There was a significant correlation between pK50 and p (octanol:buffer partition coefficient) (r2 = 0.872, P = 0.020), pK50 and p (local anaesthetic potency) (r2 = 0.816, P = 0.036), pK50 and p (relative conduction blocking potency) (r2 = 0.843, P = 0.028) and between pK50 and p (IC50 for inhibition of cardiac output) (r2 = 0.897, P = 0.015). These data suggest that DHP binding sites may be involved in both the mechanism of local anaesthesia and the cardiotoxicity of these agents. |
| | |
Authors:
|
K Hirota; T Browne; B L Appadu; D G Lambert |
Related Documents
:
|
7602609 - The effects of modulation of calcium influx through the voltage-sensitive calcium chann... 6654539 - Effects of calcium-antagonists on passive cutaneous anaphylaxis in the rat. 2435389 - Ca2+ channel ligand sensitive responses to the phorbol ester 12-o-tetradecanoylphorbol ... 21245219 - Functional comparison of plant inward-rectifier channels expressed in yeast. 17937779 - Dihydropyridine derivatives to overcome atypical multidrug resistance: design, synthesi... 2475039 - Possible inhibition of canine ventricular sarcoplasmic reticulum by bay k 8644. 10325239 - Activation of distinct camp-dependent and cgmp-dependent pathways by nitric oxide in ca... 8871099 - Accumulation of long-lasting inactivation in rat brain k(+)-channels. 8019749 - Inhibition of hypoxia-induced relaxation of rabbit isolated coronary arteries by ng-mon... |
Publication Detail:
|
Type: Journal Article |
Journal Detail:
|
Title: British journal of anaesthesia Volume: 78 ISSN: 0007-0912 ISO Abbreviation: Br J Anaesth Publication Date: 1997 Feb |
Date Detail:
|
Created Date: 1997-03-28 Completed Date: 1997-03-28 Revised Date: 2004-11-17 |
Medline Journal Info:
|
Nlm Unique ID: 0372541 Medline TA: Br J Anaesth Country: ENGLAND |
Other Details:
|
Languages: eng Pagination: 185-8 Citation Subset: IM |
Affiliation:
|
Department of Anaesthesia, Leicester Royal Infirmary. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Anesthetics, Local
/
metabolism* Animals Binding, Competitive Calcium Channels / metabolism* Calcium Channels, L-Type Cerebral Cortex / metabolism* Culture Techniques Dose-Response Relationship, Drug Female Neurons / metabolism* Rats Rats, Wistar |
| Chemical | |
Reg. No./Substance:
|
0/Anesthetics, Local; 0/Calcium Channels; 0/Calcium Channels, L-Type |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Relationship between calculated blood concentration of propofol and electrophysiological variables d...
Next Document: Effect of halothane on conventional protein kinase C translocation and down-regulation in rat cerebr...