Characterization of histamine receptors coupled to /sup 3/H-cyclic AMP accumulation in a vesicular preparation of Guinea pig cortex

Thesis/Dissertation · Tue Jan 01 00:00:00 EST 1985

OSTI ID:6709498

Newton, M V

The histamine-stimulated accumulation of /sup 3/H-cyclic AMP (formed by prelabeling with /sup 3/H-adenine) was characterized pharmacologically in a vesicular preparation of guinea pig cortex to identify the receptors mediating this response. Systematic variation of the preincubation time, vessel size, buffer composition, and /sup 3/H-adenine labeling time significantly influenced both the basal and histamine-stimulated /sup 3/H-cyclic AMP levels, and showed that individual prelabeling of aliquots in Kreb's-Ringer bicarbonate (15 mM) buffer yielded the most reproducible histamine responses. Characterization of this histamine response showed that the H/sub 2/-antagonist cimetidine maximally blocked 80% of the response, whereas only 45% of the response could be inhibited by H/sub 1/-antagonists. These findings show that both H/sub 1/- and H/sub 2/-receptors mediate the response, but 25% of the response may require concomitant activation of both receptors. A metactoid model was developed to account for the H/sub 2/-, H/sub 1/-, and adenosine components of the histamine response. The model hypothesizes that 55% of the response is due to direct H/sub 2/-receptor stimulation, 25% is dependent on the metactoid sensitization of the H/sub 2/-response by H/sub 1/-receptors, and 20% is due to an analogous sensitization of adenosine responses by H/sub 1/-receptors. These findings resolve previous controversies regarding the identity of the receptors mediating histamine-stimulated accumulation of cyclic AMP in brain. Furthermore, the vesicular preparation and metactoid model developed presently may be of benefit in other studies of neurotransmitter control of cyclic AMP dynamics.

• Research Organization: City Univ. of New York, NY (USA)
• OSTI ID: 6709498
• Resource Relation: Other Information: Thesis (Ph. D.)
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
ADENOSINE
BIOLOGICAL EFFECTS
AMP
UPTAKE
GUINEA PIGS
CEREBRAL CORTEX
HISTAMINE
RECEPTORS
ADENINES
ANTIHISTAMINICS
CALCIUM
RADIORECEPTOR ASSAY
TRITIUM COMPOUNDS
ALKALINE EARTH METALS
AMINES
ANIMALS
ANTIMETABOLITES
AROMATICS
AZAARENES
AZOLES
BODY
BRAIN
CENTRAL NERVOUS SYSTEM
CEREBRUM
DRUGS
ELEMENTS
HETEROCYCLIC COMPOUNDS
IMIDAZOLES
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
MAMMALS
MEMBRANE PROTEINS
METALS
NERVOUS SYSTEM
NUCLEOSIDES
NUCLEOTIDES
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
PROTEINS
PURINES
RIBOSIDES
RODENTS
TRACER TECHNIQUES
VERTEBRATES
550301* - Cytology- Tracer Techniques