Ca2+ utilization in guinea pig ileal longitudinal smooth muscle in response to a series of muscarinic agonists

1979 ◽  
Vol 57 (12) ◽  
pp. 1375-1380 ◽  
Author(s):  
L. B. Rosenberger ◽  
D. J. Triggle

45Ca uptake associated with the mechanical responses to a series of muscarinic agonists including carbachol, cis-2-methyl-4-dimethylaminomethyl-1,3-dioxolane methiodide, and three related 1,3-dioxolanes, including full and partial agonists, has been measured. Generally good agreement is found between the dose–response curves for 45Ca uptake and mechanical response, indicating that the processes of 45Ca entry, believed to be mediated through Ca2+ channels, and contractile response are closely linked. Consistent with this, partial agonists show (relative to full agonists) a reduced 45Ca uptake. The dose–response curves for carbachol-mediated contractile response and 45Ca uptake are compared with available literature data for carbachol action in the guinea pig ileal smooth muscle including binding, depolarization, and phosphatidylinositol turnover.

1989 ◽  
Vol 66 (2) ◽  
pp. 638-643 ◽  
Author(s):  
T. M. Murphy ◽  
N. M. Munoz ◽  
J. Moss ◽  
J. S. Blake ◽  
M. M. Mack ◽  
...  

We studied the secretory correlates of tracheal smooth muscle contraction caused by platelet-activating factor (PAF) in nine mongrel dogs in vivo. In five dogs, dose-response curves were generated by rapid intra-arterial injection of 10(-10) to 10(-6) mol PAF into the isolated tracheal circulation; tracheal contractile response was measured isometrically in situ. To examine the mechanism by which PAF elicits contraction of canine trachealis, concentrations of serotonin (5-HT) and histamine were assayed in the venous effluent as the arteriovenous difference (AVd) in mediator concentration across the airway for each level of contraction. PAF caused dose-related active tracheal tension to a maximum of 37.2 +/- 5.4 g/cm (10(-6) mol PAF). The AVd in 5-HT increased linearly from 0.20 +/- 0.05 (10(-9) mol PAF) to 3.5 +/- 0.3 ng/ml (10(-6) mol PAF) (P less than 0.005). In contrast, the AVd in histamine was insignificant and did not change with increasing doses of PAF. A positive correlation was obtained between the AVd in 5-HT and active tracheal tension (r = 0.92, P less than 0.001); there was no correlation between AVd in histamine and active tension (r = -0.16). PAF-induced parasympathetic activation was not mediated by 5-HT; contraction elicited by exogenous 5-HT was not affected by muscarinic blockade. We conclude that nonparasympathetically mediated contraction elicited acutely by PAF in dogs results at least in part from secondary release of serotonin and is not mediated by histamine.


1981 ◽  
Vol 241 (4) ◽  
pp. H557-H563 ◽  
Author(s):  
J. M. Price ◽  
D. L. Davis ◽  
E. B. Knauss

Dose-response curves were obtained from dog anterior tibial artery rings at various lengths (L) to determine whether sensitivity to norepinephrine (NE) and potassium (K+) depends on arterial circumference. The dose for half maximal response (ED50) was determined by graphical estimation and by calculation from a best fit curve. For both NE and K+: 1) ED50 was lowest (most sensitive) at L for maximum active force (Lmax) and increased significantly as L decreased from Lmax; 2) ED50 at 1.0 and 1.15 Lmax was not significantly different; 3) ED50 of repeated dose-response curves at Lmax was not significantly different; and 4) when the direction of length change was reversed (from decreasing to increasing), the direction of change in ED50 was also reversed (from increasing to decreasing). Change in the dose for 10% maximal response was the same as ED50. The results did not depend on the method of determining ED50 or on whether responses were expressed as absolute values or as relative values. The results show that sensitivity of vascular smooth muscle depends on L and that the length-sensitivity relation is similar to the length-active tension relation. Similarity of results for NE and K+ indicate that length-dependent sensitivity does not depend on the method of stimulation.


2005 ◽  
Vol 98 (5) ◽  
pp. 1603-1606 ◽  
Author(s):  
Robert H. Brown ◽  
William Wizeman ◽  
Christopher Danek ◽  
Wayne Mitzner

A recent study has reported that the application of thermal energy delivered through a bronchoscope (bronchial thermoplasty) impairs the ability of airway smooth muscle to shorten in response to methacholine (MCh)(Danek CJ, Lombard CM, Dungworth DL, Cox PG, Miller JD, Biggs MJ, Keast TM, Loomas BE, Wizeman WJ, Hogg JC, and Leff AR. J Appl Physiol 97: 1946–1953, 2004). If such a technique is successful, it has the potential to serve as a therapy to attenuate airway narrowing in asthmatic subjects regardless of the initiating cause that stimulates the smooth muscle. In the present study, we have applied high-resolution computed tomography to accurately quantify the changes in airway area before and after a standard MCh aerosol challenge in airways treated with bronchial thermoplasty. We studied a total of 193 airways ranging from 2 to 15 mm in six dogs. These were divided into treated and control populations. The MCh dose-response curves in untreated airways and soon-to-be-treated airways were superimposable. In contrast, the dose-response curves in treated airways were shifted upward at all points, showing a significantly decreased sensitivity to MCh at both 2 and 4 wk posttreatment. These results thus show that treated airways have significantly increased luminal area at any dose of inhaled MCh compared with untreated airways. The work in this study thus supports the underlying concept that impairing the smooth muscle may be an effective treatment for asthma.


1991 ◽  
Vol 69 (6) ◽  
pp. 805-811 ◽  
Author(s):  
K. Tomioka ◽  
J. T. Jackowski ◽  
W. M. Abraham

We have investigated the effects of leukotrienes (LTs) on isolated tracheal smooth muscle from sheep sensitive to Ascaris suum antigen. LTC4 and LTD4 produced dose-dependent contractions of sheep trachea, but LTE4 was virtually inactive. YM-17690, a non-analogous LT agonist, produced no contractile response up to 100 μM. Indomethacin (5 μM) had no effect on LTC4- and LTD4-induced contractions. L-Serine borate (45 mM), an inhibitor of γ-glutamyl transpeptidase, shifted the dose–response curve of LTC4 to the left by 161-fold, and L-cysteine (6 mM), an inhibitor of aminopeptidase, shifted the dose–response curves of LTC4 and LTD4 to the left by 67- and 23-fold, respectively. YM-16638 (1 μM), an LT antagonist, shifted the dose–response curves of LTC4 and LTD4 to the right with pKB values of 6.57 and 7.13, respectively. YM-16638 did not affect LTC4-induced contractions of L-serine borate-treated tissues, indicating that the compound acts only on LTD4 receptors in sheep trachea. LTE4 (1 μM) shifted the dose–response curves of LTC4 and LTD4 to the right with pKB values of 6.87 and 7.31, respectively. YM-17690 (10 μM) showed effects similar to LTE4, suggesting that the compound acts as an LTE4 agonist in sheep trachea. These results suggest that in sheep tracheal smooth muscle (a) LTC4 and LTD4 produce contractions, (b) these LT-induced contractions are not mediated by cyclooxygenase products, (c) LTC4 is converted to LTD4 and then to LTE4, and (d) the potency of the LTC4- and LTD4-induced contractions is increased when their conversion to LTE4 is inhibited. This potentiation may result from the inability of LTE4 to contract sheep trachea and (or) its antagonist actions.Key words: leukotriene antagonist, receptors, asthma.


1975 ◽  
Vol 229 (6) ◽  
pp. 1635-1640 ◽  
Author(s):  
BT Altura ◽  
BM Altura

This study, with isolated rat aortic strips and portal veins, was undertaken to : 1) study the effects, if any, of pentobarbital Na (PTB) (5 x 10(-5) to 2 X 10(-3) M) on reactivity to epinephrine, serotonin, and KCl; 2) determine whether certain concentrations of PTB induce direct actions on aortic strips and portal veins; and 3) gain some insight into how these effects are brought about. The results indicate that PTB can: a) inhibit development of spontaneous mechanical activity in these vessels in anesthetic concentrations; b) dose-dependently attenuate contractions induced by epinephrine, serotonin, and KC1; c) cause a noncompetitive type displacement of the dose response curves of these vasoactive agents; d) attenuate Ca2+- induced contractions of potassium-depolarized aortic strips and portal veins concomitant with a dose-dependent displacement of these dose-response curves to the right; and e) rapidly relax drug as well as Ca2+ -induced contractions of aortas and portal veins. In addition, the data indicate that rat portal venous smooth muscle is more sensitive to the inhibitory actions of PTB than rat aortic smooth muscle. Overall, these data suggest that concentrations of PTB used to induce surgical anesthesia can exert profound depressant effects on at least two different types of vascular smooth muscle that may be related to actions on movement and/or translocation of Ca2+.


2007 ◽  
Vol 2 (7) ◽  
pp. 1934578X0700200 ◽  
Author(s):  
Siddharth Pandey ◽  
Om Prakash ◽  
Anjum Zafar ◽  
Subrata K. Hore ◽  
Anil K. Pant ◽  
...  

Analysis of the essential oil from the rhizome of Alpinia calcarata Rosc. (ACREO) by a combination of GC and GC-MS revealed the presence of 1,8-cineole (42.2%), endo-fenchyl acetate (14.7%), camphene (7.6%), β-pinene (6.9%), α-terpineol (5.3%) and camphor (5.0%). Twenty-three compounds were identified in the oil. ACREO showed dose dependent myorelaxant activity in rat duodenum. The dose response curves of acetylcholine (ACh) and CaCl2 were shifted by ACREO to the right with increases in EC50 values and decreases in Vmax. These findings suggest that ACREO is a non-competitive antagonist of ACh and calcium.


1983 ◽  
Vol 245 (3) ◽  
pp. H379-H384 ◽  
Author(s):  
J. M. Price ◽  
D. L. Davis ◽  
E. B. Knauss

Previous work has shown that vascular smooth muscle sensitivity depends on muscle length (arterial circumference) at lengths equal to and less than that for maximum active force (Lmax). In the present study dose-response curves were obtained from dog anterior tibial artery rings at lengths equal to or longer than Lmax. The curves were compared with dose-response curves obtained at lengths less than Lmax. The agonist concentration for half maximal response (ED50) was determined by graphical estimation and by calculation from a best-fit curve. The results show that with norepinephrine (NE) stimulation 1) ED50 decreased significantly at each step when the rings were stretched from Lmax to 1.15 Lmax and then to 1.30 Lmax; 2) ED50 increased significantly when length was decreased from 1.15 to 1.00 Lmax; 3) ED50 decreased significantly at each step when the rings were stretched from 0.70 Lmax to Lmax and then to 1.30 Lmax; and 4) for NE concentration greater than the ED50 at Lmax, active stress was significantly higher at Lmax than at 0.70 Lmax or 1.30 Lmax. For an NE concentration less than the ED50 at Lmax, the active stress at 1.30 Lmax was higher than the active stress at Lmax and at 0.70 Lmax. The results show that sensitivity of vascular smooth muscle continually increases with stretch and does not have a maximum at the length for maximum active force.


1988 ◽  
Vol 254 (2) ◽  
pp. G210-G216 ◽  
Author(s):  
D. S. Louie ◽  
C. Owyang

Motilin has a stimulating effect on gastrointestinal motility. The mechanism of its action is not known. Direct and neuronal effects have been postulated. To determine if receptors are present on smooth muscle cells we investigated the effect of synthetic porcine motilin and its interaction with acetylcholine on isolated guinea pig gastric smooth muscle cells. Motilin elicited a dose-dependent contraction of gastric smooth muscle cells. Minimal (8.3 +/- 1.3%) and maximal (33.9 +/- 2.4%) responses were observed at 10(-12) and 10(-6) M, respectively. The ED50 of motilin was 10(-9) M. Acetylcholine also elicited a dose-response muscle contraction with a maximal response observed at 10(-7) M. Atropine (10(-7) M) completely inhibited the maximal response to acetylcholine but did not have any effect on the contractile response to motilin. In addition, dibutyryl guanosine 3',5'-cyclic monophosphate (10(-3) M) and substance P antagonist, spantide (10(-4) M), also did not inhibit the action of motilin. Acetylcholine (10(-11) M) shifted the dose-response curve of motilin to the left by 1.5 log units. The maximal response to the combination of motilin (10(-6) M) and acetylcholine (10(-11) M) was 32 +/- 3.2%, which was similar to the maximal response to motilin alone. It is concluded that distinct motilin and muscarinic receptors are present on guinea pig gastric smooth muscle cells. The interaction between motilin and acetylcholine is additive and not potentiative.


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