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Titolo:
CHARACTERIZATION OF THE HISTAMINE-H2-RECEPTOR STRUCTURAL COMPONENTS INVOLVED IN DUAL SIGNALING
Autore:
WANG LD; HOELTZEL M; GANTZ I; HUNTER R; DELVALLE J;
Indirizzi:
UNIV MICHIGAN,DIV GASTROENTEROL,MED CTR,MSRB-1,BOX 0682 ANN ARBOR MI 48109 UNIV MICHIGAN,DIV GASTROENTEROL,MED CTR ANN ARBOR MI 48109 UNIV MICHIGAN,DEPT INTERNAL MED,MED CTR ANN ARBOR MI 48109 UNIV MICHIGAN,DEPT SURG,MED CTR ANN ARBOR MI 48109
Titolo Testata:
The Journal of pharmacology and experimental therapeutics
fascicolo: 2, volume: 285, anno: 1998,
pagine: 573 - 578
SICI:
0022-3565(1998)285:2<573:COTHSC>2.0.ZU;2-G
Fonte:
ISI
Lingua:
ENG
Soggetto:
BETA-ADRENERGIC-RECEPTOR; SYNTHETIC PEPTIDES; INTRACELLULAR LOOP; G-PROTEINS; BETA-2-ADRENERGIC RECEPTOR; CYTOPLASMIC DOMAINS; COUPLING DOMAIN; GASTRIC GLANDS; IDENTIFICATION; REGIONS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
35
Recensione:
Indirizzi per estratti:
Citazione:
L.D. Wang et al., "CHARACTERIZATION OF THE HISTAMINE-H2-RECEPTOR STRUCTURAL COMPONENTS INVOLVED IN DUAL SIGNALING", The Journal of pharmacology and experimental therapeutics, 285(2), 1998, pp. 573-578

Abstract

We previously demonstrated that the histamine H2 receptor can activate both adenylate cyclase (AC) and phospholipase C (PLC) signaling pathways via separate GTP- dependent mechanisms. We examined whether H2 receptor-specific peptides corresponding to the amino (N) or carboxyl terminus (C) of the second (2i) or third (3i) intracytoplasmic loops or the carboxyl terminal tail (P4iN) could effect histamine- stimulated AC and PLC activity in cell membranes prepared from HEPA cells stably transfected to express the canine H2 histamine receptor cDNA. Tiotidinebinding and basal signaling were not altered by the synthetic peptides. H2P2iN, H2P2iC, H2P3iN and H2P4iN did not effect histamine stimulated AC activity although H2P3iC (10(-4) M) significantly inhibited thisparameter (65.6 +/- 7.2% of maximal stimulation) (n = 6). Combinationof the five peptides (H2P2iN, H2P2iC, H2P3iN, H2P3iC and H2P4iN) abolished histamine stimulated AC activity. Although all of the peptides inhibited histamine-stimulated PLC activity to a moderate degree individually, H2P3iC (10(-4) M) had the greatest effect, decreasing PLC activation to 20.8 +/- 6.3% of maximal stimulation (IC50 = 7.5 x 10(-7) M)(n = 6). H2P3iC and the peptide combination did not alter, forskolin,GTP gamma s or epinephrine-stimulated AC activity nor GTP gamma s andvasopressin-stimulated PLC. These studies demonstrate that both the second and third intracytoplasmic loops of the histamine H2 receptor are linked to separate signaling pathways in a differential manner.

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Documento generato il 29/09/20 alle ore 00:42:02