Synergism between ouabain and monensin in neurogenic responses of guinea-pig vas deferens

1988 ◽  
Vol 66 (5) ◽  
pp. 643-647 ◽  
Author(s):  
Takeshi Katsuragi ◽  
Lulu Kuratomi ◽  
Koji Miyamoto ◽  
Tatsuo Furukawa
Keyword(s):  
Guinea Pig ◽  
Time Course ◽  
Vas Deferens ◽  
Contractile Activity ◽  
Atpase Inhibitor ◽  
Exchange System ◽  
Deficient Medium ◽  
Small Contraction ◽  
Monensin A ◽  
Stimulation Of

Interrelations between ouabain, a Na+–K+ ATPase inhibitor, and monensin, a Na+ ionophore, on noradrenaline liberation and contractile activity were evaluated in the guinea-pig vas deferens. Monensin (1 μM) per se elicited a small contraction of the tissue. However, amplitude and time to the peak of large and sustained contractions evoked by 10 μM ouabain were potentiated and markedly shortened, respectively, by monensin. Contractions elicited by ouabain with or without monensin were prevented by 3 μM phentolamine or by pretreatment with reserpine. Contractions evoked by K+-free solution were augmented by monensin. In an HPLC study, noradrenaline outflow from the vas deferens was moderately and considerably increased by monensin (10 μM) and ouabain (100 μM), respectively. The ouabain-evoked output of noradrenaline was enhanced in the presence of monensin and the time course for maximum noradrenaline release was shortened, as was the contractile activity. This enhanced outflow after ouabain plus monensin was reserpine sensitive but not tetrodotoxin sensitive. Furthermore, this noradrenaline outflow was roughly halved in Na+-deficient medium, but was unaltered in Ca2+-free medium. These findings suggest that the synergistic effect of ouabain and monensin on noradrenaline liberation from the guinea-pig vas deferens may be due to an elevation of cytoplasmic Ca2+ concentrations, presumably resulting from a stimulation of intracellular Na+–Ca2+ exchange system, but not enhanced Ca2+ entry.

Calcium antagonists and contractile responses in rat vas deferens and guinea pig ileal smooth muscle

1979 ◽  
Vol 57 (8) ◽  
pp. 804-818 ◽  
Author(s):  
C. R. Triggle ◽  
V. C. Swamy ◽  
D. J. Triggle
Keyword(s):  
Guinea Pig ◽  
Dose Response ◽  
Calcium Antagonists ◽  
Response Curve ◽  
Vas Deferens ◽  
Contractile Activity ◽  
Rat Vas Deferens ◽  
Dose Response Curve ◽  
Tonic Component ◽  
High K

The effect of depletion of extracellular Ca2+ (Ca2+ext) on the loss of responsiveness of the guinea pig ileal longitudinal muscle (g.p.i.l.m.) and the rat vas deferens (r.v.d.) to K+ and cis-2-methyl-4-dimethylaminomethyl-1,3-dioxolane methiodide (CD), and K+ and noradrenaline (NA), has been examined and compared with the effects of a variety of local anesthetics and calcium antagonists. The results indicate that qualitative similarities are apparent with respect to the dependence of agonist-induced activity on Ca2+ext in both the g.p.i.l.m. and r.v.d. Distinct differences, however, in the Ca2+ translocation processes in these two tissues, in response to the different agonists, can be shown by the use of a variety of 'calcium antagonists' thus indicating that such translocation processes are both tissue and agonist selective.It is thus noted that, contrary to the Ca2+ depletion studies, D 600 and the usually more potent BAY-1040 showed no discrimination of action or potency in their ability to inhibit components of the NA response in the r.v.d. In contrast, D 600 and the more potent BAY-1040 selectively inhibited the tonic component of the K+ response. Treatment with SKF 525A and parethoxycaine (PC) in the g.p.i.l.m. and SKF 525A in the r.v.d. resulted in a nonselective inhibition of responses of the tissues to all stimulants. However, in the r.v.d. PC potentiated NA action, and its methobromide (MeBr) derivative potentiated both NA and K+ action and also, like PC, partially shifted to the left the dose-response curve to Ca2+ in NA-depolarizing Ca-free Tyrode's. The quaternary MeBr and the tertiary 2-chloroethyl (2Cl) derivatives of SKF 525A and PC were selectively more effective against CD- than K+-supported contractile activity in the g.p.i.l.m. and the 2Cl derivatives were more effective against NA than K+ responses in the r.v.d. The 2Cl derivative of PC also was more effective in antagonizing the Ca2+ dose–response curve in high-CD or high-NA than in high-K+ Ca2+-free Tyrode's.

Thapsigargin defines roles of Ca2+ in initial, sustained, and potentiated stimulation of pepsinogen secretion

1994 ◽  
Vol 266 (4) ◽  
pp. G613-G623 ◽  
Author(s):  
Y. Kitsukawa ◽  
C. Felley ◽  
D. C. Metz ◽  
R. T. Jensen
Keyword(s):  
Guinea Pig ◽  
Initial Phase ◽  
Time Course ◽  
Initial Increase ◽  
Cholecystokinin Octapeptide ◽  
Chief Cells ◽  
Pepsinogen Secretion ◽  
Inositol 1,4,5 Trisphosphate ◽  
Stimulation Of ◽  
Sustained Increase

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)

scholarly journals A steady-state mechanism can account for the properties of inositol 2,4,5-trisphosphate-stimulated Ca2+ release from permeabilized L1210 cells

1993 ◽  
Vol 289 (3) ◽  
pp. 861-866 ◽  
Author(s):  
J W Loomis-Husselbee ◽  
A P Dawson
Keyword(s):  
Steady State ◽  
Small Proportion ◽  
Time Course ◽  
Initial Rate ◽  
Atpase Inhibitor ◽  
Efflux Rate ◽  
Rapid Phase ◽  
L1210 Cells ◽  
Low Concentrations ◽  
Stimulation Of

We have investigated the effects of sub-maximal Ins(2,4,5)P3 concentrations on the Ca2+ permeability of the residual undischarged Ca2+ stores in electroporated or digitonin-permeabilized L1210 cells by measuring Ca(2+)-efflux rate after addition of the ATPase inhibitor thapsigargin. Low concentrations of Ins(2,4,5)P3, causing rapid discharge of a small proportion of the releasable Ca2+, result in a substantial stimulation of Ca2+ efflux after thapsigargin addition. This indicates firstly that in the absence of thapsigargin there must have been a substantial, counterbalancing, increase in rate of Ca2+ pumping, and secondly that the increased Ca2+ permeability is more consistent with a steady state than with a quantal model of Ca2+ release. Similar increases in passive Ca2+ permeability are produced by addition of concentrations of ionomycin which produce equivalent changes in Ca2+ loading to those produced by Ins(2,4,5)P3, although the time course and initial rate of Ca2+ release are very much slower. In the presence of a Ca(2+)-buffering system, the time course of Ca2+ release by Ins(2,4,5)P3 becomes superimposable on that of ionomycin, indicating that the initial rapid phase of Ins(2,4,5)P3-stimulated Ca2+ is at least partially due to positive feedback from extravesicular Ca2+.

scholarly journals Characterization of the ATPase released during sympathetic nerve stimulation of the guinea-pig isolated vas deferens

2000 ◽  
Vol 129 (8) ◽  
pp. 1684-1688 ◽  
Author(s):  
T D Westfall ◽  
S Sarkar ◽  
N Ramphir ◽  
D P Westfall ◽  
P Sneddon ◽  
...  
Keyword(s):  
Guinea Pig ◽  
Nerve Stimulation ◽  
Sympathetic Nerve ◽  
Vas Deferens ◽  
Sympathetic Nerve Stimulation ◽  
Stimulation Of
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