α-Adrenoceptor agonists and the Ca2+-dependence of smooth muscle contraction: evidence for subtypes of receptors or for agonist-dependent differences in the agonist-receptor interaction?

1985 ◽  
Vol 68 (s10) ◽  
pp. 55s-63s ◽  
Author(s):  
John C. McGrath
Keyword(s):  
Smooth Muscle ◽  
Muscle Contraction ◽  
Continuous Spectrum ◽  
Contractile Response ◽  
Nitrilotriacetic Acid ◽  
Smooth Muscle Contraction ◽  
Receptor Type ◽  
Receptor Interaction ◽  
Initial Transient ◽  
Adrenoceptor Agonists

1. The effects of varying [Ca2+]o on the contraction of smooth muscle by different α-adrenoceptor agonists were examined on rat isolated anococcygeus muscle. Agonists were tested in the presence of various [Ca2+]o or ‘Ca2+-re-addition curves’ were constructed. In some experiments the [Ca2+]free was buffered with EGTA and nitrilotriacetic acid. The components of the response which were revealed were further analysed by using drugs which modify Ca2+ mobilization. 2. Three separate elements in the contractile response were identified: (i) an initial transient contraction, due to intracellular Ca2+ release could be isolated with [Ca2+]o between 1 nmol/l and 3 μmol/l (this could be obtained only with noradrenaline, phenylephrine and amidephrine); (ii) a nifedipine-sensitive response requiring [Ca2+]o of 3 μmol/l or more; (iii) a nifedipine-resistant response requiring [Ca2+]o of 100 μmol/l or more. Presumably (ii) and (iii) involve the entry of Ca2+o: they could be obtained with all agonists tested, including these above, methoxamine, indanidine and xylazine. 3. The results are discussed in relation to the possibility of distinct types of response and their relationship to subgroups of receptors or agonists. It is concluded that there is a continuous spectrum of activity across the agonist range and that this is likely to correlate with ‘efficacy’ at a single α1 receptor type.

Effect of Desmodium adscendens fractions on antigen- and arachidonic acid-induced contractions of guinea pig airways

1988 ◽  
Vol 66 (6) ◽  
pp. 820-825 ◽  
Author(s):  
Marian E. Addy ◽  
John F. Burka
Keyword(s):  
Arachidonic Acid ◽  
Smooth Muscle ◽  
Guinea Pig ◽  
Muscle Contraction ◽  
Aqueous Extract ◽  
Contractile Response ◽  
Late Phase ◽  
Smooth Muscle Contraction ◽  
Pharmacologically Active ◽  
Active Substances

Three fractions (n-butanol, F2, and L5), isolated from an aqueous extract of Desmodium adscendens, a plant used in Ghana for the management of asthma, were evaluated for their pharmacological activity using ovalbumin and arachidonic acid-induced contractions of guinea pig airways. All three fractions inhibited the ovalbumin-induced contractions of indomethacin-pretreated tracheal spirals from sensitized animals dose dependently, but only L5 and n-butanol inhibited such contractions in the absence of indomethacin. The concentrations required to inhibit ovalbumin-induced contractions of lung parenchymal strips were threefold higher than with trachea. The contractile response over a 60-min period was divided into three phases. F2 and n-butanol inhibited all phases, whereas L5 inhibited only the late phase. n-Butanol and L5 inhibited arachidonic acid-induced contractions on indomethacin-pretreated tracheal spirals, a leukotriene-dependent reaction. There was no inhibition of arachidonic acid-induced contractions of lung parenchymal strips, which is largely a thromboxane-dependent reaction. The results suggest that D. adscendens contains several pharmacologically active substances that can inhibit allergic airway smooth muscle contraction at multiple sites, including the synthesis and (or) activity of the bronchoconstrictor leukotrienes.

Contribution of intracellular calcium to gallbladder smooth muscle contraction

1990 ◽  
Vol 259 (1) ◽  
pp. G1-G5 ◽  
Author(s):  
L. M. Renzetti ◽  
M. B. Wang ◽  
J. P. Ryan
Keyword(s):  
Smooth Muscle ◽  
Sarcoplasmic Reticulum ◽  
Ethylene Glycol ◽  
Muscle Contraction ◽  
Contractile Response ◽  
Smooth Muscle Contraction ◽  
Physiological Salt Solution ◽  
Tetraacetic Acid ◽  
Optimal Length ◽  
Ethanesulfonic Acid

Studies were performed to evaluate the contribution of intracellular Ca2+ to gallbladder smooth muscle contraction under acetylcholine (ACh) or potassium stimulation. Gallbladder smooth muscle strips from adult guinea pigs were placed in tissue baths containing N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid (HEPES)-buffered physiological salt solution (PSS) and set to optimal length for contraction (Lo). The results were as follows, 1) A 20-min equilibration in zero Ca2(+)-0.1 mM ethylene glycol-bis( beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA) PSS virtually abolished the response to potassium but not to ACh. 2) Substitution of strontium, an inhibitor of intracellular Ca2+ release, for Ca2+ significantly decreased the contractile response to ACh (3 X 10(-5), 10(-4), and 3 X 10(-4) M). Strontium had no effect on the response to 40 and 80 mM potassium. 3) Intracellular Ca2+ depletion significantly decreased gallbladder smooth muscle contraction to ACh (10(-4) M) but had no effect on the response to potassium (80 mM). 4) Ryanodine, a compound that inhibits Ca2+ storage by the sarcoplasmic reticulum, significantly decreased the contractile response to ACh (10(-4) M) but not to potassium (80 mM). These data support the observation that the use of intracellular Ca2+ by gallbladder smooth muscle for contraction is agonist dependent.

A limited rote for leukotrienes and platelet-activating factor in food protein induced jejunal smooth muscle contraction in sensitized rats

1991 ◽  
Vol 69 (12) ◽  
pp. 1841-1846 ◽  
Author(s):  
R. B. Scott ◽  
M. Maric
Keyword(s):  
Smooth Muscle ◽  
Muscle Contraction ◽  
Receptor Antagonist ◽  
Contractile Response ◽  
Platelet Activating Factor ◽  
Smooth Muscle Contraction ◽  
Food Protein ◽  
Lipoxygenase Inhibitor ◽  
Leukotriene Receptor ◽  
Web 2086

To determine whether the release of newly formed mediators such as the peptidoleukotrienes and platelet-activating factor might modulate the food protein induced jejunal smooth muscle contraction observed in sensitized rats, Hooded–Lister rats were sensitized by injection of ovalbumin (10 μg i.p.) and controls were sham sensitized with saline. Fourteen days later the contractility of longitudinally (n = 9) and circularly (n = 9) oriented jejunal segments (mucosa intact) were examined in standard tissue baths in response to antigen, leukotrienes, and platelet-activating factor alone and in the presence of a specific leukotriene receptor antagonist (MK-571), a 5-lipoxygenase inhibitor (L651,392), and a platelet-activating factor receptor antagonist (WEB 2086). Although the responses of control and sensitized tissues to stretch and 10−4 M bethanechol were similar, only sensitized tissues contracted in response to antigen (1 mg/mL). MK-571 (10−5 M) reduced or significantly inhibited the contractile response of sensitized longitudinally and circularly oriented tissues to 10−7 M leukotrienes C4, D4, or E4, but neither L651,392 (10−4 M) nor MK-571 (10−5 M) significantly reduced the contractile response of sensitized tissues to antigen challenge. WEB 2086 (10−4 M) significantly (p < 0.01) reduced the contractile response of sensitized longitudinally and circularly oriented tissues to 10−7 M platelet-activating factor but did not significantly alter the response to antigen in longitudinally (45% of control, p = 0.14) or circularly (118% of control, ns) oriented jejunal smooth muscle. In this model leukotrienes and platelet-activating factor play an insignificant role in modulating food protein induced jejunal smooth muscle contraction in intestinal anaphylaxis.Key words: leukotrienes, platelet-activating factor, smooth muscle, anaphylaxis, food allergy.

Ectopic expression of caveolin-1 restores physiological contractile response of aged colonic smooth muscle

2007 ◽  
Vol 293 (1) ◽  
pp. G240-G249 ◽  
Author(s):  
Sita Somara ◽  
Robert R. Gilmont ◽  
Jeffrery R. Martens ◽  
Khalil N. Bitar
Keyword(s):  
Signal Transduction ◽  
Smooth Muscle ◽  
Muscle Contraction ◽  
Contractile Response ◽  
Colonic Motility ◽  
Smooth Muscle Contraction ◽  
Membrane Microdomains ◽  
Aged Rats ◽  
Wild Type ◽  
Caveolin 1

Reduced colonic motility has been observed in aged rats with a parallel reduction in acetylcholine (ACh)-induced myosin light chain (MLC20) phosphorylation. MLC20 phosphorylation during smooth muscle contraction is maintained by a coordinated signal transduction cascade requiring both PKC-α and RhoA. Caveolae are membrane microdomains that permit rapid and efficient coordination of different signal transduction cascades leading to sustained smooth muscle contraction of the colon. Here, we show that normal physiological contraction can be reinstated in aged colonic smooth muscle cells (CSMCs) upon transfection with wild-type caveolin-1 through the activation of both the RhoA/Rho kinase and PKC pathways. Our data demonstrate that impaired contraction in aging is an outcome of altered membrane translocation of PKC-α and RhoA with a concomitant reduction in the association of these molecules with the caveolae-specific protein caveolin-1, resulting in a parallel decrease in the myosin phosphatase-targeting subunit (MYPT) and CPI-17 phosphorylation. Decreased MYPT and CPI-17 phosphorylation activates MLC phosphatase activity, resulting in MLC20 dephosphorylation, which may be responsible for decreased colonic motility in aged rats. Importantly, transfection of CSMCs from aged rats with wild-type yellow fluorescent protein-caveolin-1 cDNA restored translocation of RhoA and PKC-α and phosphorylation of MYPT, CPI-17, and MLC20, thereby restoring the contractile response to levels comparable with young adult rats. Thus, we propose that caveolin-1 gene transfer may represent a promising therapeutic treatment to correct the age-related decline in colonic smooth muscle motility.

Role of phosphoinositide metabolism in functional antagonism of airway smooth muscle contraction by β-adrenoceptor agonists

1989 ◽  
Vol 172 (2) ◽  
pp. 175-183 ◽  
Author(s):  
Ronald G.M. Van Amsterdam ◽  
Herman Meurs ◽  
Frans Brouwer ◽  
Jan Bert Postema ◽  
Adiet Timmermans ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Muscle Contraction ◽  
Airway Smooth Muscle ◽  
Smooth Muscle Contraction ◽  
Phosphoinositide Metabolism ◽  
Adrenoceptor Agonists ◽  
Functional Antagonism

Calcium and Vascular Smooth Muscle Contraction

1971 ◽  
Vol 28 (5 Suppl 2) ◽  
pp. II-88-II-95 ◽  
Author(s):  
CHARLES L. SEIDEL ◽  
DAVID F. BOHR
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Muscle Contraction ◽  
Smooth Muscle Contraction ◽  
Vascular Smooth Muscle Contraction
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