Muscarinic antagonist binding to intact rat thymocytes

Acta Chem Scand (Cph). 1990 Feb;44(2):147-51. doi: 10.3891/acta.chem.scand.44-0147.

Abstract

The presence and properties of muscarinic receptors on intact rat thymocytes have been studied by the use of the muscarinic antagonists [3H]-3-quinuclidinyl benzilate (3H-QNB), [3H]-4-N-methylpiperidinyl benzilate ([3H]-NMBP) and [3H]-N-methylscopolamine (3H-NMS). The course of binding of 3H-QNB reveals a maximum at 5 min, and shows a subsequent decrease of bound radioactivity, suggesting internalization of the receptor 3H-3-QNB complex. This phenomenon has also been studied by the use of another muscarinic antagonist, 3H-NMPB, which has a faster on and off rate than 3H-QNB, and which may be rapidly displaced by an excess of unlabeled muscarinic antagonist, atropine. Bound 3H-NMPB is highly susceptible to atropine displacement only within the first two minutes of incubation with thymocytes at 37 degrees C. The kinetics of binding of the less lipophilic muscarinic antagonist 3H-NMS to thymocytes, show no maximum as a function of incubation time and 3H-NMS is susceptible to displacement by atropine up to 30 min incubation time with the thymocytes. These data suggest that binding of lipophilic benzilate type antagonists (3H-QNB and 3H-NMPB) may be followed by internalization and/or isomerization of the receptor-benzilate antagnist complex while the 3H-NMS-receptor complex is not subject to these processes.

MeSH terms

  • Animals
  • Atropine / metabolism
  • Benzilates*
  • Kinetics
  • Male
  • Muscarine / antagonists & inhibitors*
  • N-Methylscopolamine
  • Piperidines / metabolism
  • Quinuclidinyl Benzilate / metabolism
  • Rats
  • Rats, Inbred Strains
  • Receptors, Muscarinic / metabolism*
  • Scopolamine Derivatives / metabolism
  • Thymus Gland / metabolism*

Substances

  • Benzilates
  • Piperidines
  • Receptors, Muscarinic
  • Scopolamine Derivatives
  • Quinuclidinyl Benzilate
  • Atropine
  • Muscarine
  • enpiperate
  • N-Methylscopolamine