In vitro nasal transport across ovine mucosa: effects of ammonium glycyrrhizinate on electrical properties and permeability of growth hormone releasing peptide, mannitol, and lucifer yellow.
Transport of growth hormone releasing peptide across ovine nasal mucosa in the absence or presence of ammonium glycyrrhizinate (AMGZ) was studied in vitro. Ovine nasal mucosa was stripped from underlying cartilage and mounted in Ussing chambers. Transepithelial conductance (Gt) and short-circuit current (Isc) were monitored during experiments to assess tissue viability and integrity. Radiolabeled mannitol (Man; MW 182) and growth hormone releasing peptide (GHRP, SK&F 110679; MW 873) were employed to measure transport rates across the epithelium, and fluorescence spectroscopy was employed to measure rates of lucifer yellow (LY; MW 521) transport. Effects of AMGZ on ovine nasal mucosal viability and transport were determined from changes in electrical properties of fluxes of [3H]GHRP, [3H]Man, and LY. Results demonstrate that electrical properties of ovine nasal mucosa are stable over the time course of the experiments (Gt = 8.3 +/- 0.5 mS/cm2 and Isc = 3.7 +/- 0.2 microEq/hr.cm2; n = 21). Man fluxes were comparable in the mucosal (m)-to-serosal (s) and s-to-m directions [0.10 +/- 0.01 (n = 17) and 0.10 +/- 0.01 (n = 4) %/hr.cm2, respectively]. Transport of GHRP and LY in the m-s direction was similar to that of Man [0.08 +/- 0.01 (n = 11) and 0.09 +/- 0.01 (n = 3) %/hr.cm2, respectively]. GHRP flux was equivalent in the m-s and s-m directions. GHRP did not significantly alter ion transport processes as indicated by the lack of any change in Gt or Isc.(ABSTRACT TRUNCATED AT 250 WORDS)
Reardon
P M
PM
Department of Pharmaceutical Chemistry, University of Kansas, Lawrence 66045.
Gochoco
C H
CH
Audus
K L
KL
Wilson
G
G
Smith
P L
PL
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D004553:Electric Conductivity / Q000187:drug effects; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism; D006034:Glycyrrhetinic Acid / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D019695:Glycyrrhizic Acid; D013007:Growth Hormone-Releasing Hormone / Q000493:pharmacokinetics*; D066298:In Vitro Techniques; D007546:Isoquinolines / Q000493:pharmacokinetics*; D008353:Mannitol / Q000493:pharmacokinetics*; D009297:Nasal Mucosa / Q000187:drug effects / Q000378:metabolism*; D010634:Phenobarbital / Q000378:metabolism / Q000494:pharmacology; D012756:Sheep
D007546:Isoquinolines; D008353:Mannitol; D019695:Glycyrrhizic Acid; D013007:Growth Hormone-Releasing Hormone; C017475:lucifer yellow; D006034:Glycyrrhetinic Acid; D010634:Phenobarbital