PMID- 8179000
OWN - NLM
STAT- MEDLINE
DCOM- 19940609
LR  - 20181130
IS  - 0002-9513 (Print)
IS  - 0002-9513 (Linking)
VI  - 266
IP  - 4 Pt 1
DP  - 1994 Apr
TI  - Thapsigargin defines roles of Ca2+ in initial, sustained, and potentiated 
      stimulation of pepsinogen secretion.
PG  - G613-23
AB  - The roles of Ca2+ in agonist-induced pepsinogen secretion from guinea pig chief 
      cells remain unclear. We used cholecystokinin octapeptide (CCK-8) or secretin 
      alone or with thapsigargin (TG) to clarify these roles. TG releases Ca2+ from 
      intracellular stores by inhibiting microsomal Ca(2+)-adenosinetriphosphatase 
      (ATPase), thereby depleting intracellular Ca2+ (Cai2+) stores. In most cells TG 
      also causes Ca2+ influx. In the present study, with an extracellular Ca2+ 
      concentration ([Ca2+]o) of 1.5 mM, CCK-8 (0.1 microM) caused a rapid increase in 
      pepsinogen secretion; however, the rate decreased with time. With [Ca2+]o = 0, 
      the initial increase was similar but later secretion was abolished, suggesting 
      that Ca2+ influx was important for sustained secretion. With [Ca2+]o = 1.5 mM, TG 
      (0.1 microM) caused a 2.7-fold sustained increase in in Cai2+ concentration 
      ([Ca2+]i) and a ninefold sustained increase in pepsinogen secretion. With [Ca2+]o 
      = 0, TG caused a transient 66% increase in [Ca2+]i and a 50% increase in 
      pepsinogen secretion. The time course of TG-induced pepsinogen secretion 
      correlated with the time course of TG-induced increases in [Ca2+]i. These data 
      demonstrated that Ca2+ influx itself was a potent stimulant of pepsinogen 
      secretion. We further focused on the roles of increasing [Ca2+]i from Cai2+ 
      stores. With or without extracellular Ca2+ (Cao2+) present, addition of CCK-8 
      (0.1 microM) 10 min after TG caused no further increase in [Ca2+]i, demonstrating 
      depletion of the inositol 1,4,5-trisphosphate-sensitive pool. The 
      Ca(2+)-mobilizing agent CCK-8 caused no pepsinogen secretion 10 min after TG 
      preincubation, demonstrating that mobilization of Ca2+ from intracellular stores 
      was important in the rapid initial phase stimulation of pepsinogen secretion 
      caused by CCK-8. In contrast, preincubation with TG had no effect on pepsinogen 
      secretion by secretin, an agent that increases adenosine 3',5'-cyclic 
      monophosphate. A 6-min preincubation with TG potentiated the subsequent 
      stimulation of pepsinogen secretion caused by secretin in the presence of Cao2+ 
      where [Ca2+]i remained elevated. However, TG-induced potentiations of 
      secretin-stimulated pepsinogen secretion was abolished once [Ca2+]i had returned 
      to the basal level in the absence of Cao2+.(ABSTRACT TRUNCATED AT 400 WORDS)
FAU - Kitsukawa, Y
AU  - Kitsukawa Y
AD  - Digestive Diseases Branch, National Institute of Diabetes and Digestive and 
      Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892.
FAU - Felley, C
AU  - Felley C
FAU - Metz, D C
AU  - Metz DC
FAU - Jensen, R T
AU  - Jensen RT
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Am J Physiol
JT  - The American journal of physiology
JID - 0370511
RN  - 0 (Pepsinogens)
RN  - 0 (Plant Extracts)
RN  - 0 (Terpenes)
RN  - 1393-25-5 (Secretin)
RN  - 67526-95-8 (Thapsigargin)
RN  - M03GIQ7Z6P (Sincalide)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Animals
MH  - Calcium/*physiology
MH  - Dose-Response Relationship, Drug
MH  - Drug Synergism
MH  - Gastric Mucosa/cytology/*metabolism
MH  - Guinea Pigs
MH  - Kinetics
MH  - Male
MH  - Pepsinogens/*metabolism
MH  - Plant Extracts/pharmacology
MH  - Secretin/pharmacology
MH  - Sincalide/pharmacology
MH  - Terpenes/*pharmacology
MH  - Thapsigargin
EDAT- 1994/04/01 00:00
MHDA- 1994/04/01 00:01
CRDT- 1994/04/01 00:00
PHST- 1994/04/01 00:00 [pubmed]
PHST- 1994/04/01 00:01 [medline]
PHST- 1994/04/01 00:00 [entrez]
AID - 10.1152/ajpgi.1994.266.4.G613 [doi]
PST - ppublish
SO  - Am J Physiol. 1994 Apr;266(4 Pt 1):G613-23. doi: 10.1152/ajpgi.1994.266.4.G613.