Tolerance Following Organophosphate Poisoning of Tracheal Muscle
Abstract
The tritiated muscarinic cholinergic antagonist quinuclidinyl benzilate ((3H)QNB) was used to characterize the muscarinic receptors associated with membranes prepared from swine tracheal smooth muscle. As judged from receptor-binding assays, the membrane homogenate had specific high-affinity receptors for (3H)QNB. Specific binding was saturable with respect to (3H)QNB and tissue concentrations and was time- and pH-dependent. The association of (3H)QNB (180 pM) with the muscarinic receptors reached equilibrium much sooner at 37 C than 25 C (30 min and 2 hrs, respectively). Equilibrium at both temperatures was attained within 5 min at a high concentration of (3H)QNB, 1800 pM. All other experiments were performed at 37 C. Analysis of binding isotherms yielded an apparent equilibrium dissociation constant (K sub D) of 51 + or - 20 pM and a maximum receptor density (B max) of 2.17 + or - 0.27 pmole/mg protein. The Hill coefficient for (3H)QNB binding was 1.07 + or - 0.16. The association and dissociation rate constants were determined to be (5.51 + or - 0.16) x 100, 000,000/M/min and (1.41 + or - 0.18) x .01/min, respectively. The muscarinic antagonists atropine and scopolamine competitively inhibited (3H)QNB binding to the homogenate, with a Hill coefficient of 0.9 and inhibition constant of 1.8 NM. Muscarinic agonists and the nicotinic antagonist d-tubocurare inhibited (3H) QNB binding in micromolar concentrations. Tolerance to daily diisopropylfluoro phosphonate (DFP) injection was observed in these animals.
Document Details
- Document Type
- Technical Report
- Publication Date
- Dec 13, 1984
- Accession Number
- ADB100950
Entities
People
- Jerry M. Farley
- Terry M. Dwyer
Organizations
- University of Mississippi Medical Center