Affinities of pirenzepine for muscarinic cholinergic receptors in membranes isolated from bovine tracheal mucosa and smooth muscle

Journal Article · Sat Feb 28 23:00:00 EST 1987 · Am. Rev. Respir. Dis.; (United States)

OSTI ID:6576994

Madison, J M; Jones, C A; Tom-Moy, M; Brown, J K

Muscarinic cholinergic receptors have been classified into subtypes based on their high (M-1 subtype) or low (M-2 subtype) affinities for the nonclassic antagonist pirenzepine, and this classification has important experimental and therapeutic implications. Because muscarinic receptors are abundant in the airways where they mediate several different cellular responses, the goal of this study was to characterize the affinities of pirenzepine for the muscarinic receptors in bovine tracheal mucosa and smooth muscle. After isolating membrane particulates from mucosa and smooth muscle, as well as from bovine cerebral cortex (a known source of M-1 receptors), we used /sup 3/H-quinuclidinyl benzilate to label muscarinic receptors in the particulates and performed competition radioligand binding assays in the presence of either atropine or pirenzepine. Receptors from all 3 tissues (mucosa, smooth muscle, and cerebral cortex) were of a relatively uniform affinity for atropine (range of KI values: 0.8 +/- 0.4 X 10(-9) to 2.4 +/- 1.7 X 10(-9) M), as would be predicted for this classic muscarinic antagonist. By contrast, affinities for pirenzepine differed depending on the tissue. In cerebral cortex, the majority of receptors were of high affinity for pirenzepine (KI = 1.8 +/- 1.4 X 10(-8) M). In both mucosa and smooth muscle, receptors were of low affinity for pirenzepine (Kl = 4.8 +/- 0.4 to 6.9 +/- 3.8 X 10(-7) M). We conclude that muscarinic cholinergic receptors in bovine tracheal mucosa and smooth muscle are predominantly of the M-2 subtype.

• Research Organization: Veterans Administration Medical Center, San Francisco, CA
• OSTI ID: 6576994
• Journal Information: Am. Rev. Respir. Dis.; (United States), Journal Name: Am. Rev. Respir. Dis.; (United States) Vol. 3; ISSN ARDSB
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
AFFINITY
ALCOHOLS
AMINES
AMMONIUM COMPOUNDS
ANIMALS
BIOCHEMICAL REACTION KINETICS
BODY
BRAIN
CATTLE
CELL CONSTITUENTS
CELL MEMBRANES
CENTRAL NERVOUS SYSTEM
CENTRAL NERVOUS SYSTEM AGENTS
CEREBRAL CORTEX
CEREBRUM
CHOLINE
CLASSIFICATION
DOMESTIC ANIMALS
DRUGS
HYDROXY COMPOUNDS
IN VITRO
ISOTOPE APPLICATIONS
KINETICS
LABELLED COMPOUNDS
LIPOTROPIC FACTORS
MAMMALS
MEMBRANE PROTEINS
MEMBRANES
MUSCLES
NERVOUS SYSTEM
ORGANIC COMPOUNDS
ORGANS
PROTEINS
PSYCHOTROPIC DRUGS
QUATERNARY COMPOUNDS
RADIOASSAY
REACTION KINETICS
RECEPTORS
RESPIRATORY SYSTEM
RUMINANTS
TRACER TECHNIQUES
TRACHEA
TRANQUILIZERS
TRITIUM COMPOUNDS
VERTEBRATES