Interactions of the local anesthetic tetracaine with membranes containing phosphatidylcholine and cholesterol: a /sup 2/H NMR study

Journal Article · Tue Jun 28 00:00:00 EDT 1988 · Biochemistry; (United States)

OSTI ID:7039589

Auger, M; Jarrell, H C; Smith, I C.P.

The interactions of local anesthetic tetracaine with multilamellar dispersions of 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) and cholesterol have been investigated by deuterium nuclear magnetic resonance of specifically deuteriated tetracaines, DMPC and cholesterol. Experiments were performed at pH 5.5, when the anesthetic is primarily charged, and at pH 9.5, when it is primarily uncharged. The partition coefficients of the anesthetic in the membrane have been measured at both pH values for phosphatidylcholine bilayers with and without cholesterol. The higher partition coefficients obtained at pH 9.5 reflect the hydrophobic interactions between the uncharged form of the anesthetic and the hydrocarbon region of the bilayer. The lower partition coefficients for the DMPC/cholesterol system at both pH values suggest that cholesterol, which increases the order of the lipid chains, decreases the solubility of tetracaine into the bilayer. For phosphatidylcholine bilayers, it has been proposed that the charged tetracaine at low pH is located mostly at the phospholipid headgroup level while the uncharged tetracaine intercalates more deeply into the bilayer. The present study suggests that the location of tetracaine in the cholesterol-containing system is different from that in pure phosphatidylcholine bilayers: the anesthetic sits higher in the membrane. An increase in temperature results in a deeper penetration of the anesthetic into the bilayer. Moreover, the incorporation of the anesthetic into DMPC bilayers with or without cholesterol results in a reduction of the lipid order parameters both in the plateau and in the tail regions of the acyl chains, this effect being greater with the charged form of the anesthetic.

• Research Organization: National Research Council of Canada, Ottawa, Ontario
• OSTI ID: 7039589
• Journal Information: Biochemistry; (United States), Vol. 27:13
• Country of Publication: United States
• Language: English

Related Subjects

62 RADIOLOGY AND NUCLEAR MEDICINE
ANTIBIOTICS
BIOCHEMISTRY
CONFIGURATION INTERACTION
NUCLEAR MAGNETIC RESONANCE
CELL MEMBRANES
CHOLESTEROL
DEUTERIUM COMPOUNDS
PHOSPHOLIPIDS
ANTI-INFECTIVE AGENTS
CELL CONSTITUENTS
CHEMISTRY
DRUGS
ESTERS
HYDROGEN COMPOUNDS
HYDROXY COMPOUNDS
LIPIDS
MAGNETIC RESONANCE
MEMBRANES
ORGANIC COMPOUNDS
ORGANIC PHOSPHORUS COMPOUNDS
RESONANCE
STEROIDS
STEROLS
550601* - Medicine- Unsealed Radionuclides in Diagnostics