Competitive interactions between Bay K 8644 and nifedipine in K+ depolarized smooth muscle: a passive role for Ca2+?

1985 ◽  
Vol 328 (4) ◽  
pp. 464-466 ◽  
Author(s):  
Michael Spedding
Keyword(s):  
Smooth Muscle ◽  
Bay K 8644 ◽  
Competitive Interactions ◽  
Depolarized Smooth Muscle

Inhibition of dihydropyridine-sensitive calcium entry in hypoxic relaxation of airway smooth muscle

1995 ◽  
Vol 268 (2) ◽  
pp. L201-L206 ◽  
Author(s):  
C. Vannier ◽  
T. L. Croxton ◽  
L. S. Farley ◽  
C. A. Hirshman
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Muscle Tone ◽  
Bay K 8644 ◽  
O2 Concentration ◽  
Voltage Dependent ◽  
Progressive Hypoxia ◽  
Carbamyl Choline

Hypoxia dilates airways in vivo and reduces active tension of airway smooth muscle in vitro. To determine whether hypoxia impairs Ca2+ entry through voltage-dependent channels (VDC), we tested the ability of dihydropyridines to modulate hypoxia-induced relaxation of KCl- and carbamyl choline (carbachol)-contracted porcine bronchi. Carbachol- or KCl-contracted bronchial rings were exposed to progressive hypoxia in the presence or absence of 1 microM BAY K 8644 (an L-type-channel agonist). In separate experiments, rings were contracted with carbachol or KCl, treated with nifedipine (a VDC antagonist), and finally exposed to hypoxia. BAY K 8644 prevented hypoxia-induced relaxation in KCl-contracted bronchi. Nifedipine (10(-5) M) totally relaxed KCl- contracted bronchi. Carbachol-contracted bronchi were only partially relaxed by nifedipine but were completely relaxed when the O2 concentration of the gas was reduced from 95 to 0%. These data indicate that hypoxia can reduce airway smooth muscle tone by limiting entry of Ca2+ through a dihydropyridine-sensitive pathway, but that other mechanisms also contribute to hypoxia-induced relaxation of carbachol-contracted bronchi.

Dependence of stress on cross-bridge phosphorylation in vascular smooth muscle

1989 ◽  
Vol 256 (1) ◽  
pp. C96-C100 ◽  
Author(s):  
P. H. Ratz ◽  
C. M. Hai ◽  
R. A. Murphy
Keyword(s):  
Smooth Muscle ◽  
Steady State ◽  
Vascular Smooth Muscle ◽  
Light Chain ◽  
Phorbol Esters ◽  
Receptor Activation ◽  
Bay K 8644 ◽  
Cross Bridge ◽  
Cross Bridges ◽  
State Stress

Cross-bridge phosphorylation associated with agonist-stimulated contraction of vascular smooth muscle is often transiently elevated. Such observations led to the concept that phosphorylation of the 20-kDa myosin regulatory light chain (Mp) was required for initial activation and cross-bridge cycling but might not be necessary for steady-state maintenance of stress in the latch state. The possibility that stress maintenance is not regulated by phosphorylation has received some experimental support in contractions induced by phorbol esters and the calcium channel activator BAY K 8644 in which significant increases in Mp were not detected. Our aim was to test the hypothesis that phosphorylation is both necessary and sufficient for activation and for maintenance of steady-state stress. Activation of swine carotid media using agents that bypass receptor activation and elevate Ca2+ influx without mobilizing intracellular Ca2+ stores (BAY K 8644 and ionomycin) produced monotonic increases in both stress and Mp. Transient initial peaks in Mp were absent. Steady-state stress induced by both receptor- and nonreceptor-mediated activation was dependent on small increases in Mp. Increases in Mp greater than 0.3 mol Pi/mol myosin light chain had small effects on stress but produced large increases in the maximum rate of cross-bridge cycling at zero load (Vo). The experimentally determined dependence of stress on Mp was quantitatively predicted by our working hypothesis. This model proposes that Ca2+-stimulated cross-bridge phosphorylation is obligatory for cross-bridge attachment. However, dephosphorylation of attached cross bridges to form noncycling "latch bridges" allows stress maintenance with reduced Mp and cycling.

Characterization of the effects of AHN 086, an irreversible ligand of "peripheral" benzodiazepine receptors, on contraction in guinea-pig atria and ileal longitudinal smooth muscle

1989 ◽  
Vol 67 (2) ◽  
pp. 126-134 ◽  
Author(s):  
G. T. Bolger ◽  
A. H. Newman ◽  
K. C. Rice ◽  
H. W. M. Lueddens ◽  
A. S. Basile ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Guinea Pig ◽  
Calcium Channels ◽  
Benzodiazepine Receptors ◽  
Significant Inhibition ◽  
Bay K 8644 ◽  
Longitudinal Smooth Muscle ◽  
Peripheral Benzodiazepine Receptors ◽  
Inotropic Responses ◽  
Guinea Pig Atria

The effects of AHN 086 and its reversibly acting structural analogue Ro 5-4864 were studied in the spontaneously beating guinea-pig atria and field-stimulated guinea-pig ileal longitudinal smooth muscle in the presence and absence of dihydropyridine calcium channel modulators. The treatment of guinea-pig atria with AHN 086 followed by extensive washing did not alter contraction. However, AHN 086 (0.5 μM) potentiated (88%) the positive inotropic responses by BAY K 8644, an effect that was not reversed by extensive washing of the tissue. Higher concentrations of AHN 086 (> 2 μM) irreversibly inhibited the intropic, but not the chronotropic responses to BAY K 8644, nifedipine, and isoproterenol. Ro 5-4864 (10 μM) produced a reversible enhancement of the inotropic responses and block of the chronotropic responses to BAY K 8644. In guinea-pig ileal longitudinal smooth muscle, both AHN 086 and Ro 5-4864 reversibly inhibited field-stimulated contractions. Neither Ro 5-4864 nor AHN 086 affected the ability of nifedipine to inhibit field-stimulated contractions of ileal longitudinal smooth muscle. Treatment of intact atria with 5 μM AHN 086 followed by extensive washing resulted in a significant inhibition (30–50%) of [3H]Ro 5-4864 binding to peripheral benzodiazepine receptors and of [3H]nitrendipine binding to voltage-operated calcium channels, but did not affect [3H]dihydroalprenolol binding to β-adrenergic receptors on atrial membranes. The same treatment applied to intact ileal longitudinal smooth muscle affected neither [3H] (−)-quinuclidinyl benzilate binding to muscarine receptors nor [3H]nitrendipine binding, but did result in a significant inhibition (30–50%) of [3H]Ro 5-4864 binding to ileal longitudinal smooth muscle membranes. The pharmacology of AHN 086 suggests that there is a different relationship between peripheral benzodiazepine receptors and voltage-operated calcium channels in guinea-pig atria and ileal longitudinal smooth muscle.Key words: calcium channels, peripheral benzodiazepine receptors, dihydropyridines, benzodiazepines, dihydropyridine binding sites.

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