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Histamine receptors coupled to (/sup 3/H)cAMP accumulation in brain: pharmacological characterization in a vesicular preparation of guinea pig cortex

Journal Article · · Mol. Pharmacol.; (United States)
OSTI ID:5481643
;

The histamine-stimulated accumulation of (/sup 3/H)cAMP (formed by prelabeling with (/sup 3/H)adenine) was characterized pharmacologically in a vesicular preparation of guinea pig cortex. The H2 antagonist cimetidine maximally blocked 80% of the response, whereas only 45% of the response could be inhibited by H1 antagonists. A combination of H1 and H2 antagonists completely abolished the response. These and other findings show that both H1 and H2 receptors mediate the response, but 25% of the response may require simultaneous activation of both receptors. A role for adenosine as a mediator of the histamine response was investigated. Adenosine deaminase (EC 3.5.4.4., 2.5 units/ml) decreased basal (/sup 3/H)cAMP levels, abolished the cimetidine-resistant component of the histamine response, and reduced maximal H1 antagonism of the histamine response to 30%. Treatment with a combination of adenosine deaminase and the calcium chelator EGTA (2 mM) appeared to eliminate the H1 component completely. Under these latter conditions only H2 receptors appeared to mediate the histamine response. Thus, both H1 and H2 receptors stimulate (/sup 3/H)cAMP accumulation in the vesicular preparation, but the H1 response seems to require either concomitant adenosine or H2 receptor stimulation and may be calcium dependent. These findings differ from those found in broken cell membrane preparations, where only H2 receptors appear to be coupled to adenylate cyclase activation.

Research Organization:
City Univ. of New York, NY
OSTI ID:
5481643
Journal Information:
Mol. Pharmacol.; (United States), Journal Name: Mol. Pharmacol.; (United States) Vol. 33:1; ISSN MOPMA
Country of Publication:
United States
Language:
English

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Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ADENOSINE
ALCOHOLS
AMIDINASES
AMINES
AMP
ANIMALS
AZOLES
BIOCHEMICAL REACTION KINETICS
BIOLOGICAL ACCUMULATION
BODY
BRAIN
CARBOXYLIC ACIDS
CENTRAL NERVOUS SYSTEM
CEREBRAL CORTEX
CEREBRUM
CHELATING AGENTS
EGTA
ENZYMES
GLYCOLS
GUINEA PIGS
HETEROCYCLIC COMPOUNDS
HISTAMINE
HYDROLASES
HYDROXY COMPOUNDS
IMIDAZOLES
IN VITRO
ISOTOPE APPLICATIONS
KINETICS
LABELLED COMPOUNDS
MAMMALS
MEMBRANE PROTEINS
NERVOUS SYSTEM
NON-PEPTIDE C-N HYDROLASES
NUCLEOSIDES
NUCLEOTIDES
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
PROTEINS
REACTION KINETICS
RECEPTORS
RIBOSIDES
RODENTS
TRACER TECHNIQUES
TRITIUM COMPOUNDS
VERTEBRATES