Spontaneous regeneration of free muscarinic receptor after alkylation by BM 123. I. Recovery in vivo and in cell culture.

Abstract

The recovery of rat muscarinic receptor number from the effects of a specific alkylating ligand, N-[4-(2-chloroethylmethylamino)-2-butynyl]-2-pyrrolidone (BM 123), in three tissues is presented as an exponential function of time. No significant difference was found in the recovery rate constants derived from analysis of recovery time courses in corpus striatum, cerebral cortex and ileal longitudinal muscle. The single rate constant (0.021/hr) was also independent of amount and duration of BM 123 dose. Additional analysis of agonist-defined high and low affinity subsites in cortex revealed that recovery of these populations also followed similar time courses although the alkylation proceeds more slowly for the high affinity sites. The rate constant for recovery of both subsites was 0.029/hr. Recovery from BM 123 alkylation occurred in NG108-15 neuroblastoma X glioma cells. The presence of cycloheximide in the recovery medium did not significantly inhibit this recovery process in the clonal cell line, suggesting that de novo receptor synthesis is unnecessary for regeneration of unalkylated receptors.

• Authors: J J Waite, D J Jenden
• Journal: The Journal of pharmacology and experimental therapeutics (J Pharmacol Exp Ther) Vol. 248 Issue 1 Pg. 111-8 (Jan 1989) ISSN: 0022-3565 [Print] United States
• PMID: 2913265 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Parasympatholytics
• Pyrrolidinones
• Receptors, Muscarinic
• N-(4-(2-chloroethylmethylamino)-2-butynyl)-2-pyrrolidone
• Cycloheximide

Topics

• Alkylation
• Animals
• Cells, Cultured
• Cycloheximide (pharmacology)
• Male
• Parasympatholytics (pharmacology)
• Pyrrolidinones (pharmacology)
• Rats
• Rats, Inbred Strains
• Receptors, Muscarinic (biosynthesis, drug effects, physiology)