Invariant relation between total acid secretion and secretagogue exposure: secretory dynamics in bullfrog

1984 ◽  
Vol 246 (4) ◽  
pp. G325-G330 ◽  
Author(s):  
E. B. Ekblad ◽  
V. Licko
Keyword(s):  
Acid Secretion ◽  
Response Curve ◽  
Limited Range ◽  
Secretion Rate ◽  
Invariant Relation ◽  
Total Acid ◽  
Time Integral ◽  
Ph Stat ◽  
Concentration Response Curve ◽  
Stimulation By Histamine

Using a continuous recording of acid secretion in frog gastric mucosa by pH-stat interfaced with a microcomputer, the pattern of secretion rate was studied under variable concentrations and durations of stimulation by histamine and forskolin. This tissue can respond with only a limited range of secretory rates. Larger concentrations and/or longer durations of stimulation may result in a secretion rate pattern prolonged far beyond the duration of stimulation. Although for the concentration-response curve the steady-state or peak acid secretion varies with the duration of stimulation, total acid secreted as a function of exposure to stimulator (time integral of the stimulatory pattern) is independent of the stimulatory pattern.

Cholinergic stimulation modulates negative inotropic effect of cocaine on ferret ventricular myocardium

1996 ◽  
Vol 270 (2) ◽  
pp. H678-H684
Author(s):  
L. Miao ◽  
Z. Qiu ◽  
J. P. Morgan
Keyword(s):  
Response Curve ◽  
Negative Inotropic Effect ◽  
Ventricular Myocardium ◽  
Inotropic Effect ◽  
Dependent Manner ◽  
Cholinergic Stimulation ◽  
Concentration Dependent Manner ◽  
Cell Shortening ◽  
Inotropic State ◽  
Concentration Response Curve

We tested the hypothesis that the negative inotropic effect (NIE) of cocaine is mediated, at least in part, by cholinergic stimulation and can be correlated with the degree of adenosine 3',5'-cyclic monophosphate (cAMP) dependency of the inotropic state. Cardiac myocytes were isolated from left ventricles of ferrets and loaded with the fluorescent Ca2+ indicator indo 1. Cells were placed in physiological solution containing 2.0 mM Ca2+ and stimulated at 0.5 Hz and 30 degrees C. Cocaine decreased peak cell shortening and peak intracellular Ca2+ in a concentration-dependent manner (10(-8)-10(-4) M). The concentration-response curve of cocaine was shifted significantly downward compared with those of lidocaine and procaine in the same range of concentrations. Atropine (10(-6) M) shifted the concentration-response curve of cocaine, but not those of lidocaine and procaine, rightward, with a pA2 value (7.66) similar to that obtained with carbachol (7.99). With prior addition of isoproterenol (ISO, 10(-8) M) or increased Ca2+ (4.0 mM) to increase cell shortening to the same degree (approximately 60%), cocaine and carbachol decreased contractility to a significantly greater extent in ISO-stimulated myocytes. To clarify whether these treatments changed responsiveness of the contractile elements to Ca2+, the effect of 2,3-butanedione monoxime, an agent that interferes with the interaction of myosin and actin, was tested with previous addition of ISO or increased Ca2+, and no differential effect occurred. Therefore, we postulate that 1) the NIE of cocaine on myocytes is caused by decreased Ca2+ availability; 2) this effect is due to specific stimulation of cholinergic receptors in addition to other direct myocardial (probably local anesthetic) effects; and 3) the NIE correlates with the level of cAMP dependence of the inotropic state.

scholarly journals Agonist Efficiency Estimated from Concentration Response Curve

2021 ◽  
Vol 120 (3) ◽  
pp. 57a
Author(s):  
Dinesh Indurthi ◽  
Anthony Auerbach
Keyword(s):  
Response Curve ◽  
Concentration Response Curve

BAFILOMYCIN A1 AT NANOMOLAR CONCENTRATIONS SATURABLY INHIBITS A PORTION OF TURTLE BLADDER ACIDIFICATION CURRENT

2001 ◽  
Vol 204 (16) ◽  
pp. 2911-2919
Author(s):  
STEVEN J. YOUMANS ◽  
CATHERINE R. BARRY
Keyword(s):  
Urinary Bladder ◽  
Acid Secretion ◽  
Dose Response ◽  
Response Curve ◽  
Collecting Duct ◽  
Dose Response Curve ◽  
Serosal Side ◽  
Bafilomycin A1 ◽  
Transport Activity ◽  
Turtle Bladder

SUMMARY An earlier report indicated that acid secretion in turtle urinary bladder is driven by an unusual vacuolar H+-ATPase and that the ATPase accounts for essentially all acid secreted. These results, however, are difficult to reconcile with the acid transporters currently ascribed to the renal collecting duct. Here, we re-examine the effect of bafilomycin A1, an inhibitor of vacuolar (V-type) H+-ATPases, on acid secretion by intact isolated bladders from Pseudemys scriptaturtles. Serosal-side bafilomycin had no effect on the transepithelial acidification current (AC). In the mucosal solution, bafilomycin inhibited the AC, with inhibition developing over the range 0.1-10 nmol l-1, with a sigmoidal dose—response curve, and an IC50 of 0.47 nmol l-1. At saturation, approximately 70 % of H+ secretion was inhibited. The remaining 30 % could be abolished by 30 μmol l-1 Sch-28080, which is a level that in other systems is known to inhibit H+/K+-ATPase transport activity specifically and essentially completely. When the order of addition was reversed (Sch-28080 first), there was no change in the magnitude of the effect produced by either inhibitor, and the two together again eliminated the AC. The data indicate that baseline acid secretion in intact bladders is due (i) in part to a highly bafilomycin-sensitive process, with sensitivity typical of vacuolar H+ ATPases; and (ii) in part to a more bafilomycin-resistant process that is sensitive to Sch-28080.

scholarly journals The Cellular Prion Protein Prevents Copper-Induced Inhibition of P2X4Receptors

2011 ◽  
Vol 2011 ◽  
pp. 1-6
Author(s):  
Ramón A. Lorca ◽  
Lorena Varela-Nallar ◽  
Nibaldo C. Inestrosa ◽  
J. Pablo Huidobro-Toro
Keyword(s):  
Amino Acids ◽  
Synaptic Transmission ◽  
Prion Protein ◽  
Adenosine Triphosphate ◽  
Response Curve ◽  
Physiological Function ◽  
Cellular Prion Protein ◽  
Synaptic Activity ◽  
Receptor Subtype ◽  
Concentration Response Curve

Although the physiological function of the cellular prion protein (PrPC) remains unknown, several evidences support the notion of its role in copper homeostasis. PrPCbinds Cu2+through a domain composed by four to five repeats of eight amino acids. Previously, we have shown that the perfusion of this domain prevents and reverses the inhibition by Cu2+of the adenosine triphosphate (ATP)-evoked currents in the P2X4receptor subtype, highlighting a modulatory role for PrPCin synaptic transmission through regulation of Cu2+levels. Here, we study the effect of full-length PrPCin Cu2+inhibition of P2X4receptor when both are coexpressed. PrPCexpression does not significantly change the ATP concentration-response curve in oocytes expressing P2X4receptors. However, the presence of PrPCreduces the inhibition by Cu2+of the ATP-elicited currents in these oocytes, confirming our previous observations with the Cu2+binding domain. Thus, our observations suggest a role for PrPCin modulating synaptic activity through binding of extracellular Cu2+.

gamma-Aminobutyric acid-induced response in rat dissociated paratracheal ganglion cells

1992 ◽  
Vol 67 (5) ◽  
pp. 1367-1374 ◽  
Author(s):  
S. Itabashi ◽  
K. Aibara ◽  
H. Sasaki ◽  
N. Akaike
Keyword(s):  
Response Curve ◽  
Ganglion Cells ◽  
Aminobutyric Acid ◽  
Equilibrium Potential ◽  
Induced Response ◽  
Dependent Manner ◽  
Gamma Aminobutyric Acid ◽  
Patch Clamp Technique ◽  
Concentration Dependent Manner ◽  
Concentration Response Curve

1. The pharmacologic properties of gamma-aminobutyric acid (GABA)-induced Cl- current (ICl) were studied in the paratracheal ganglion cells freshly dissociated from 7- to 10-day-old rat trachea in a whole-cell recording mode by the use of a conventional patch-clamp technique. 2. GABA- and muscimol-induced currents increased sigmoidally in a concentration-dependent manner, and both currents reversed at approximately -3 mV, which was close to the Cl- equilibrium potential (ECl). 3. Strychnine (STR) at low concentration and bicuculline (BIC) inhibited GABA response competitively, whereas STR at the higher concentrations, benzylpenicillin (PCG), or picrotoxin (PTX) inhibited noncompetitively. Inhibition of GABA response by PCG but not other antagonists was voltage dependent, indicating that PCG acts as a Cl- channel blocker. 4. The concentration-response curve of pentobarbital sodium (PB)-induced ICl was bell shaped. At concentrations higher than 10(-3) M, both the peak and plateau currents decreased, and a transient "hump" current appeared immediately after washing out PB. In the presence of PB, the concentration-response curve of GABA shifted toward left without changing the maximum response. 5. Although diazepam (DZP) at concentration used did not induce a response, it potentiated the GABA response in a concentration-dependent manner between 10(-8) and 10(-6) M. DZP also caused a parallel shift toward left in the concentration-response curve of GABA. 6. PB or DZP further enhanced the GABA response in the presence of the other agent. 7. It is concluded that the properties of GABAA receptors in the paratracheal ganglion cells are essentially similar to those reported in other preparations.

Conservative and nonconservative inhibitors of gastric acid secretion

1987 ◽  
Vol 253 (3) ◽  
pp. G359-G368 ◽  
Author(s):  
E. B. Ekblad ◽  
V. Licko
Keyword(s):  
Steady State ◽  
Acid Secretion ◽  
Initial Step ◽  
No Net Loss ◽  
Apparent Loss ◽  
H2 Antagonist ◽  
Flow Through ◽  
Ph Stat ◽  
High Concentrations ◽  
Continuous Presence

Inhibitors of the initial step (H2-antagonist) and of the final step (thiocyanate, SCN-; and nitrite, NO2-) were used to study the dynamics of acid secretion in isolated frog gastric mucosa. Tissues were mounted in flow-through chambers, and the acid secretion rate (SR) was recorded on a pH-stat microprocessor. Continuous presence of H2-antagonist decreases the SR to a lower steady state, and on removal the SR returns to basal SR, causing a net loss of acid, the nonconservative effect. The amount of lost acid is a unique function of exposure, thus, independent of the patterns (pulses or steps) of inhibition. In contrast, continuous presence of SCN- or NO2- (below 3 mM) results in an undershoot in SR with a return to basal SR, whereas at higher concentrations there is no return. Removal of these inhibitors causes an overshoot in SR with return to basal SR. The rebound acid is equal to acid suppressed by NO2- and low concentration of SCN-, resulting in no net loss of acid, the conservative effect, whereas at high concentrations of SCN- there is an apparent loss of acid. In maximally secreting tissue the overshoot of SR is not observed. However, the acid is not lost, merely delayed. In resting tissue NO2- also merely delays the exit of the acid produced in response to forskolin. The rebound acid is proposed to reside in a sequestered "acid" pool that is stable for at least 120 min. Results with NO2- and SCN- suggest an effect on a saturable exit enzyme, possibly the K+-H+-ATPase.

Renal microvascular effects of endothelin

1990 ◽  
Vol 259 (2) ◽  
pp. F217-F221 ◽  
Author(s):  
R. M. Edwards ◽  
W. Trizna ◽  
E. H. Ohlstein
Keyword(s):  
Response Curve ◽  
Contractile Response ◽  
Maximum Response ◽  
Lumen Diameter ◽  
Rabbit Kidney ◽  
Significant Shift ◽  
Efferent Arteriole ◽  
Endothelin 1 ◽  
Afferent Arterioles ◽  
Concentration Response Curve

The effects of endothelin 1, 2, and 3 (ET-1, -2, -3) on lumen diameter of individual afferent and efferent arterioles dissected from rabbit kidney were examined. ET-1 produced concentration-dependent and long-lasting decreases in lumen diameter in both arterioles. The 50% maximum response (EC50) values were 1.4 +/- 0.41 and 0.9 +/- 0.65 nM for afferent and efferent arterioles, respectively. In afferent arterioles, ET-2 produced decreases in lumen diameter (EC50 = 3.3 +/- 1.75 nM) that were indistinguishable from ET-1. However, ET-3 was considerably less potent (EC50 = 21.9 +/- 6.0 nM, P less than 0.05) than ET-1 or ET-2. Similar results were obtained in the efferent arteriole in which the EC50 for ET-2 (0.25 +/- 0.1 nM) was similar to ET-1, but ET-3 was significantly less potent (EC50 = 2.6 +/- 0.4 nM, P less than 0.05). Nicardipine (0.01-1 microM) produced concentration-dependent shifts in the ET-1 concentration-response curve in afferent arterioles. Verapamil (1 microM) also caused a significant shift in the ET-1 response curve. The contractile response to ET-1 was significantly more sensitive to nicardipine than was the response to norepinephrine. In contrast, the response of efferent arterioles to ET-1 and norepinephrine was unaffected by nicardipine or verapamil. The results demonstrate that ETs are potent vasoconstrictors of both the pre- and postglomerular microvasculature and may play a role in the regulation of renal hemodynamics.(ABSTRACT TRUNCATED AT 250 WORDS)

Superoxide anion impairs Ca2+mobilization in cultured human nasal epithelial cells

1999 ◽  
Vol 277 (6) ◽  
pp. L1089-L1095
Author(s):  
Tetsuya Koyama ◽  
Masahiro Oike ◽  
Sohtaro Komiyama ◽  
Yushi Ito
Keyword(s):  
Superoxide Dismutase ◽  
Epithelial Cells ◽  
Superoxide Anion ◽  
Response Curve ◽  
Krebs Solution ◽  
Nasal Epithelial Cells ◽  
Human Nasal Epithelial Cells ◽  
Bath Application ◽  
Intracellular Ca ◽  
Concentration Response Curve

We examined the effects of superoxide anion ([Formula: see text]) on the intracellular Ca2+ concentration in cultured human nasal epithelial cells. The cells were exposed to[Formula: see text] by pretreatment with xanthine (X) and xanthine oxidase (XO); control cells were treated with X alone. When Ca2+-containing Krebs solution was reperfused in the thapsigargin-treated, store-depleted cells, reapplication-induced intracellular Ca2+ concentration elevation was significantly smaller in X/XO-treated cells than in the control cells, suggesting that [Formula: see text] impairs Ca2+ release-activated Ca2+ entry (CRAC). Bath application of ATP induced a steep Ca2+ transient in both control and X/XO-treated cells. However, the concentration-response curve of the ATP-induced Ca2+ transient was shifted to a higher concentration in X/XO-treated cells. The impairments of CRAC and ATP-induced Ca2+ transient induced by X/XO were reversed by superoxide dismutase. Furthermore, all these X/XO-induced effects were also observed in cells pretreated with pyrogallol, also an [Formula: see text] donor. These results indicate that [Formula: see text] impairs at least two mechanisms involved in Ca2+ mobilization in human nasal epithelial cells, i.e., CRAC and ATP-induced Ca2+ release.

Acid secretion in isolated guinea pig colon

1987 ◽  
Vol 253 (2) ◽  
pp. G155-G164 ◽  
Author(s):  
Y. Suzuki ◽  
K. Kaneko
Keyword(s):  
Carbonic Anhydrase ◽  
Guinea Pig ◽  
Acid Secretion ◽  
Proximal Part ◽  
Bathing Solution ◽  
Maximal Effect ◽  
Dose Dependency ◽  
Ussing Chambers ◽  
Mucosal Acidification ◽  
Ph Stat

Isolated guinea pig distal colons secreted acid into the mucosal bathing solution at a rate of 1.0-1.5 mumol X cm-2 X h-1 when the preparations were mounted in Ussing chambers and bathed with HCO3(-)-CO2-free solution. The rates of the acidification and alkalinization of the solutions were measured by a pH stat system or calculated from changes in the pH of the solution. The acid secretion was localized in the middle and distal parts of the colon but absent in the proximal part of the colon and the cecum. The mucosal acidification was accompanied by serosal alkalinization, the rate of the latter being approximately 60% of the former. A carbonic anhydrase inhibitor, methazolamide (10(-4) M), reduced both the mucosal acidification and serosal alkalinization rates by a similar magnitude. The mucosal acidification was completely abolished by mucosal K+-free conditions but unaffected by mucosal Na+-free conditions. Ouabain added to the mucosal solution promptly inhibited the acid secretion. Dose dependency of the inhibition conformed to the Michaelis-Menten equation with a half-maximal effect at 4 X 10(-6) M. When the pH of the mucosal solution was reduced to 4.3, the rate of the mucosal acidification remained essentially the same as that at pH = 7.4. Vanadate (10(-4) M) added to both the mucosal and serosal solutions significantly reduced the mucosal acidification rate. These results suggest that CO2 derived from the epithelial metabolism is hydrated by carbonic anhydrase in the cell and released H+ enters the mucosal solution while HCO3- enters the serosal solution. H+ exit across the mucosal membrane may be mediated by H+-ATPase that is sensitive to ouabain.

scholarly journals Characterization of the concentration-response curve for ambient ozone and acute respiratory morbidity in 5 US cities

2018 ◽  
Vol 29 (2) ◽  
pp. 267-277 ◽  
Author(s):  
Vaughn Barry ◽  
Mitchel Klein ◽  
Andrea Winquist ◽  
Howard H. Chang ◽  
James A. Mulholland ◽  
...  
Keyword(s):  
Response Curve ◽  
Respiratory Morbidity ◽  
Ambient Ozone ◽  
Us Cities ◽  
Concentration Response Curve
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