HISTAMINE H-1 RECEPTOR-INDUCED CA2- POSSIBLE ROLE OF RECEPTOR-OPERATED CA2+ INFLUX( MOBILIZATION AND PROSTAGLANDIN E(2) RELEASE IN HUMAN GINGIVAL FIBROBLASTS )
N. Niisato et al., HISTAMINE H-1 RECEPTOR-INDUCED CA2- POSSIBLE ROLE OF RECEPTOR-OPERATED CA2+ INFLUX( MOBILIZATION AND PROSTAGLANDIN E(2) RELEASE IN HUMAN GINGIVAL FIBROBLASTS ), Biochemical pharmacology, 52(7), 1996, pp. 1015-1023
Stimulation of human gingival fibroblasts with histamine elicited an i
ncrease in the intracellular concentration of free calcium ([Ca2+](i))
and the formation of inositol 1,4,5-trisphosphate (InsP(3)) in a conc
entration- and time dependent manner. The histamine-induced increase i
n [Ca2+](i) was attenuated completely by chlorpheniramine, an H-1 anta
gonist, but not by cimetidine, an H-2 antagonist. The histamine-induce
d Ca2+ response consisted of an initial transient peak response and a
subsequent sustained increase. The transient phase can be largely attr
ibuted to Ca2+ release from intracellular InsP(3)-sensitive stores sin
ce the increased [Ca2+](i) effect of histamine completely disappeared
after depletion of intracellular Ca2+ stores with thapsigargin in the
absence of extracellular Ca2+. The sustained phase was due to Ca2+ inf
lux which was attenuated in the absence of extracellular Ca2+. The Ca2
+ influx required the continuous binding of histamine to the receptor,
since chlorpheniramine attenuated the increase in [Ca2+](i) observed
when extracellular Ca2+ was re-applied to the cells after stimulation
with histamine in the absence of extracellular Ca2+. Pretreatment with
the Ca2+ channel blocker SK&F96365 inhibited the Ca2+ influx componen
t, suggesting that histamine stimulates Ca2+ influx through an H-1 rec
eptor-operated Ca2+ channel. Histamine also evoked a concentration- an
d time-dependent release of prostaglandin E(2) (PGE(2)). The histamine
-evoked PGE(2) release was reduced markedly by exclusion of extracellu
lar Ca2+ or pretreatment with SK&F96365 or an H-1 antagonist. These re
sults indicate that histamine stimulates both the intracellular Ca2+ r
elease from InsP, sensitive stores and the H-1 receptor-operated Ca2influx from extracellular sites. The increased [Ca2+](i) due to the Ca
2+ influx causes PGE(2) release in human gingival fibroblasts.