scholarly journals A novel role for calmodulin: Ca2+-independent inhibition of type-1 inositol trisphosphate receptors

1998 ◽  
Vol 334 (2) ◽  
pp. 447-455 ◽  
Author(s):  
Thomas J. A. CARDY ◽  
Colin W. TAYLOR
Keyword(s):  
Spodoptera Frugiperda ◽  
Inhibitory Effect ◽  
Ip3 Receptors ◽  
Inhibitory Effects ◽  
Independent Manner ◽  
S 100 ◽  
High Concentrations ◽  
Type 3 ◽  
Stimulation Of

Calmodulin inhibits both inositol 1,4,5-trisphosphate (IP3) binding to, and IP3-evoked Ca2+ release by, cerebellar IP3 receptors [Patel, Morris, Adkins, O'Beirne and Taylor (1997) Proc. Natl. Acad. Sci. U.S.A. 94, 11627–11632]. In the present study, full-length rat type-1 and -3 IP3 receptors were expressed at high levels in insect Spodoptera frugiperda 9 cells and the effects of calmodulin were examined. In the absence of Ca2+, calmodulin caused a concentration-dependent and reversible inhibition of [3H]IP3 binding to type-1 IP3 receptors by decreasing their apparent affinity for IP3. The effect was not reproduced by high concentrations of troponin C, parvalbumin or S-100. Increasing the medium free [Ca2+] ([Ca2+]m) inhibited [3H]IP3 binding to type-1 receptors, but the further inhibition caused by a submaximal concentration of calmodulin was similar at each [Ca2+]m. In the absence of Ca2+, 125I-calmodulin bound to a single site on each type-1 receptor subunit and to an additional site in the presence of Ca2+. There was no detectable binding of 125I-calmodulin to type-3 receptors and binding of [3H]IP3 was insensitive to calmodulin at all [Ca2+]m. Both peptide and conventional Ca2+–calmodulin antagonists affected neither [3H]IP3 binding directly nor the inhibitory effect of calmodulin in the absence of Ca2+, but each caused a [Ca2+]m-dependent reversal of the inhibition of [3H]IP3 binding caused by calmodulin. Camstatin, a peptide that binds to calmodulin equally well in the presence or absence of Ca2+, reversed the inhibitory effects of calmodulin on [3H]IP3 binding at all [Ca2+]m. We conclude that calmodulin specifically inhibits [3H]IP3 binding to type-1 IP3 receptors: the first example of a protein regulated by calmodulin in an entirely Ca2+-independent manner. Inhibition of type-1 IP3 receptors by calmodulin may dynamically regulate their sensitivity to IP3 in response to the changes in cytosolic free calmodulin concentration thought to accompany stimulation of neurones.

In Vitro Effects of Ethanol on Rabbit Platelet Aggregation, Secretion of Granule Contents, and Cyclic AMP Levels in the Presence of Prostacyclin

1989 ◽  
Vol 61 (02) ◽  
pp. 254-258 ◽  
Author(s):  
Margaret L Rand ◽  
Peter L Gross ◽  
Donna M Jakowec ◽  
Marian A Packham ◽  
J Fraser Mustard
Keyword(s):  
Cyclic Amp ◽  
Inhibitory Effect ◽  
Rabbit Platelet ◽  
Inhibitory Effects ◽  
Low Concentrations ◽  
Rabbit Platelets ◽  
High Concentrations ◽  
In Vitro Effects ◽  
Aggregation Of Platelets

SummaryEthanol, at physiologically tolerable concentrations, inhibits platelet responses to low concentrations of collagen or thrombin, but does not inhibit responses of washed rabbit platelets stimulated with high concentrations of ADP, collagen, or thrombin. However, when platelet responses to high concentrations of collagen or thrombin had been partially inhibited by prostacyclin (PGI2), ethanol had additional inhibitory effects on aggregation and secretion. These effects were also observed with aspirin- treated platelets stimulated with thrombin. Ethanol had no further inhibitory effect on aggregation of platelets stimulated with ADP, or the combination of ADP and epinephrine. Thus, the inhibitory effects of ethanol on platelet responses in the presence of PGI2 were very similar to its inhibitory effects in the absence of PGI2, when platelets were stimulated with lower concentrations of collagen or thrombin. Ethanol did not appear to exert its inhibitory effects by increasing cyclic AMP above basal levels and the additional inhibitory effects of ethanol in the presence of PGI2 did not appear to be brought about by further increases in platelet cyclic AMP levels.

scholarly journals Highly Oxygenated Triterpenoids and Diterpenoids from Fructus Rubi (Rubus Chingii Hu) and Their NF-kappa B Inhibitory Effects

Molecules ◽  
2021 ◽  
Vol 26 (7) ◽  
pp. 1911
Author(s):  
Jiang Wan ◽  
Xiao-Juan Wang ◽  
Nan Guo ◽  
Xi-Ying Wu ◽  
Juan Xiong ◽  
...  
Keyword(s):  
Inhibitory Effects ◽  
Nf Kappa B ◽  
Pentacyclic Triterpenoids ◽  
Chemical Structures ◽  
Phytochemical Investigation ◽  
Ic50 Values ◽  
Rubus Chingii ◽  
Rubus Chingii Hu ◽  
Type 3

During a phytochemical investigation of the unripe fruits of Rubus chingii Hu (i.e., Fructus Rubi, a traditional Chinese medicine named “Fu-Pen-Zi”), a number of highly oxygenated terpenoids were isolated and characterized. These included nine ursane-type (1, 2, and 4–10), five oleanane-type (3, 11–14), and six cucurbitane-type (15–20) triterpenoids, together with five ent-kaurane-type diterpenoids (21–25). Among them, (4R,5R,8R,9R,10R,14S,17S,18S,19R,20R)-2,19α,23-trihydroxy-3-oxo-urs-1,12-dien-28-oic acid (rubusacid A, 1), (2R*,4S*,5R*,8R*,9R*,10R*,14S*,17S*, 18S*,19R*,20R*)-2α,19α,24-trihydroxy-3-oxo-urs-12-en-28-oic acid (rubusacid B, 2), (5R,8R,9R,10R, 14S,17R,18S,19S)-2,19α-dihydroxy-olean-1,12-dien-28-oic acid (rubusacid C, 3), and (3S,5S,8S,9R, 10S,13R,16R)-3α,16α,17-trihydroxy-ent-kaur-2-one (rubusone, 21) were previously undescribed. Their chemical structures and absolute configurations were elucidated on the basis of spectroscopic data and electronic circular dichroism (ECD) analyses. Compounds 1 and 3 are rare naturally occurring pentacyclic triterpenoids featuring a special α,β-unsaturated keto-enol (diosphenol) unit in ring A. Cucurbitacin B (15), cucurbitacin D (16), and 3α,16α,20(R),25-tetrahydroxy-cucurbita-5,23- dien-2,11,22-trione (17) were found to have remarkable inhibitory effects against NF-κB, with IC50 values of 0.08, 0.61, and 1.60 μM, respectively.

PKC-independent inhibition of cardiac L-type Ca2+ channel current by phorbol esters

1996 ◽  
Vol 270 (2) ◽  
pp. H620-H627 ◽  
Author(s):  
T. Asai ◽  
L. M. Shuba ◽  
D. J. Pelzer ◽  
T. F. McDonald
Keyword(s):  
Protein Kinase C ◽  
Phorbol Esters ◽  
Ventricular Myocytes ◽  
Inhibitory Effect ◽  
Independent Action ◽  
Independent Manner ◽  
Channel Current ◽  
Kinase C ◽  
Channel Currents ◽  
Stimulation Of

Active and inactive phorbol esters were applied to guinea pig ventricular myocytes to study the responses of L-type Ca2+ (ICa,L) and L-type Na+ (INa,L) currents. Phorbol 12-myristate 13-acetate (PMA) (10-100 rM) never stimulated ICa,L or INa,L and frequently depressed them by 5-30% in a voltage-independent manner. However, the phorbol ester consistently activated delayed-rectifying K+ (IK) and Cl- currents. The inhibition of ICa,L occurred approximately 3 times faster than comonitored stimulation of IK, and ICa,L and INa,L were unaffected by two interventions that suppressed IK stimulation [pretreatment with 50 microM 1-(5-isoquinolinesulfonyl)-2-methylpiperazine (H-7) and dialysis with pCa 11 versus standard pCa 9 solution]. Inactive phorbol esters 4 alpha-phorbol 12,13-didecanoate (alpha-PDD) and 4 alpha-phorbol had little effect on IK, but alpha-PDD had a PMA-like inhibitory effect on Ca2+ channel currents. We conclude that, unlike the stimulation of IK by PMA, inhibition of Ca2+ channel current by phorbol esters is a protein kinase C-independent action.

scholarly journals Afferent Stochastic Modulation of Crayfish Caudal Photoreceptor Units

1968 ◽  
Vol 51 (4) ◽  
pp. 534-551 ◽  
Author(s):  
Howard T. Hermann ◽  
Richard E. Olsen
Keyword(s):  
Inhibitory Effect ◽  
Fiber Optic Probe ◽  
Inhibitory Effects ◽  
Excitatory Effect ◽  
Multiple Pulses ◽  
Caudal Photoreceptor ◽  
Stochastic Modulation ◽  
The Mean ◽  
Optic Probe ◽  
Stimulation Of

When all roots to the sixth ganglion of the crayfish are cut, the caudal photoreceptor unit (PRU) fires at regular intervals. With an intact preparation, stimulation of caudal tactile hairs has predominantly inhibitory effects on the PRU: short bursts of afferent impulses, produced by momentary mechanical stimulation of tactile hairs, have (a) occasional immediate excitatory effect on the PRU, (b) prolonged inhibitory effect. The mean firing rate of the afferented and deafferented PRUs reacts similarly to a step increase in light, but the same unit fires faster after deafferentation. In the dark, deafferented units often fire paired or multiple pulses; the interval between pulses in a pair is similar to the short mode in afferented histograms. A fiber-optic probe of the caudal ganglion demonstrates the approximate location of the photosensitive element.

Effects of heavy metals and other trace elements on the fermentative activity of the rumen microflora and growth of functionally important rumen bacteria

1978 ◽  
Vol 24 (3) ◽  
pp. 298-306 ◽  
Author(s):  
C. W. Forsberg
Keyword(s):  
Trace Elements ◽  
Rumen Fluid ◽  
Inhibitory Effect ◽  
Rumen Bacteria ◽  
Inhibitory Effects ◽  
Butyrivibrio Fibrisolvens ◽  
Fermentative Activity ◽  
Rumen Microflora ◽  
High Concentrations

The inhibitory effects of high concentrations of essential and non-essential trace elements were tested on the rumen microflora using the rate of fermentation in vitro as the assay. The elements (and the concentration causing 50% inhibition) in decreasing order of toxicity were Hg2+ (20 μg/ml), Cu2+ (21 μg/ml), Cr6+ (70 μg/ml), Se4+ (73 μg/ml), Ni2+ (160 μg/ml), Cd2+ (175 μg/ml), As3+ (304 μg/ml), and As5+ (1610 μg/ml). The elements tested that were either weak or non-inhibitory at concentrations greater than 400 μg/ml included Zn2+, Cr2+, Fe2+, Mn2+, Pb2+, and Co2+. Methylmercury was as inhibitory as mercuric chloride to the fermentation. When the inhibitory effect of Cd2+ was tested on separated bacterial and protozoal fractions, it was more inhibitory to the bacteria. The inhibitory effects of trace elements were also determined for a number of axenic cultures of rumen bacteria. The bacteria which most frequently exhibited the greatest sensitivity were Bacteroides succinogenes, Ruminococcus albus, Bacteroides amytophilus, and Eubacterium ruminantium. Those often exhibiting intermediate sensitivities included Butyrivibrio fibrisolvens, Selenomonas niminantium, and Megasphera elsdenii, while Streptococcus bovis was very refractory to all elements tested. Rumen fluid provided a modest protective effect for the bacteria.

Potentiation of Adrenaline-Induced Platelet Aggregation by Angiotensin II

1985 ◽  
Vol 54 (03) ◽  
pp. 717-720 ◽  
Author(s):  
Yu-An Ding ◽  
D Euan MacIntyre ◽  
Christopher J Kenyon ◽  
Peter F Semple
Keyword(s):  
Platelet Aggregation ◽  
Angiotensin Ii ◽  
Human Platelet ◽  
Inhibitory Effect ◽  
Facilitatory Effect ◽  
Ang Ii ◽  
Human Platelet Aggregation ◽  
Low Concentrations ◽  
High Concentrations ◽  
Stimulation Of

SummaryThe effects of angiotensin II (ANG II) alone and in combination with other agonists on human platelet aggregation, thromboxane B2 (TxB2) and cytosolic [Ca2+]i were investigated. ANG II (10™11 - 10™7 M) alone had no direct effect on aggregation, TxB2 production or [Ca2+]i after short- (<2 min) or longterm (30 min) incubation. In contrast, low concentrations of ANG II (10™11 M) enhanced adrenaline-induced platelet aggregation but high concentrations (10™7 M) had an inhibitory effect. Moreover, ANG II (10™11 - 10™7 M) augmented platelet responses to the TxA2 mimetic, U44069. Pretreatment of platelets with flurbiprofen abolished this facilitatory effect of ANG II on adrenaline- but not on U44069-induced platelet aggregation. These results suggest that ANG II stimulation of agonist-induced platelet activation may be due to potentiation of the effects rather than the synthesis of TxA2

Failure of 16,16-dimethyl PGE2 to prevent inhibitory effect of ethanol on sodium transport in canine gastric mucosa

1985 ◽  
Vol 248 (3) ◽  
pp. G299-G306
Author(s):  
T. A. Miller ◽  
J. M. Henagan ◽  
Y. J. Kuo ◽  
L. L. Shanbour
Keyword(s):  
Gastric Mucosa ◽  
Sodium Transport ◽  
Short Circuit ◽  
Short Circuit Current ◽  
Inhibitory Effect ◽  
Gastric Epithelium ◽  
Bathing Solution ◽  
Inhibitory Effects ◽  
Stimulation Of

By use of an in vitro canine gastric mucosal preparation, we evaluated the effects of ethanol (2, 4, 6, and 8%, vol/vol) and indomethacin (2.2 X 10(-4)M), with and without 16,16-dimethyl PGE2 pretreatment, on net sodium transport (JNanet) (mucosal to serosal) across gastric epithelium. Although administration of 2 or 4% ethanol to the mucosal bathing solution had no appreciable inhibitory effects on sodium transport, 6 and 8% ethanol and indomethacin significantly inhibited JNanet when compared with untreated control mucosa. This effect was accompanied by inhibition of transmucosal potential difference (PD) and short-circuit current (Isc). In other mucosae exposed to dimethyl PGE2 (8 X 10(-6) M) in the serosal bathing solution, significant increases in JNanet, PD, and Isc were noted when compared with control mucosa. Addition of 6 or 8% ethanol to the mucosal solution of dimethyl PGE2-pretreated tissue resulted in significant decreases in PD, Isc, and JNanet below control values that were not significantly different from mucosa exposed to 6 and 8% ethanol without PG pretreatment. When indomethacin was added to the mucosal solution following dimethyl PGE2 pretreatment, only slight decreases in PD and Isc below control levels were observed, and the inhibitory effects on JNanet induced by indomethacin without such treatment were abolished. These findings suggest that stimulation of JNanet by prostaglandin may play a role in its ability to prevent indomethacin damage to gastric epithelium but does not appear to be of importance in mediating protection against ethanol damage.

scholarly journals THE USE OF FORMALDEHYDE-TREATED 131I-ALBUMIN IN THE STUDY OF DIGESTIVE VACUOLES AND SOME PROPERTIES OF THESE PARTICLES FROM MOUSE LIVER

1967 ◽  
Vol 32 (3) ◽  
pp. 699-707 ◽  
Author(s):  
John L. Mego ◽  
Francisco Bertini ◽  
J. Donald McQueen
Keyword(s):  
Trichloroacetic Acid ◽  
Mouse Liver ◽  
Inhibitory Effect ◽  
Protein Hydrolysis ◽  
Cathepsin Activity ◽  
High Concentrations ◽  
Triton X ◽  
Hydrolysis Of ◽  
High Sucrose ◽  
Stimulation Of

The trichloroacetic acid-soluble radioactivity released during incubation of mouse liver particles containing intravenously injected formaldehyde-treated 131I-albumin consisted almost entirely of 131I-iodotyrosine. The material was shown to be excreted into the medium and was not due to disruption of the particles by acid. Triton X-100 or the absence of sucrose in the medium inhibited hydrolysis of the particle-associated labeled protein. This inhibition was due to disruption of the digestive vacuoles and dilution of the protein and cathepsins in the suspending medium. These results and other experimental evidence strongly suggest that the 131I-albumin-containing liver particles are digestive vacuoles. The results also establish that 131I-albumin may be used to study these vacuoles. High concentrations of sucrose (1 M) inhibited degradation of intraparticulate protein. However, 1 M salts inhibited only the rate of the digestion. Sucrose had an inhibitory effect on a crude cathepsin preparation, and salts stimulated the activity when 131I-albumin was used as substrate. The effect of high sucrose concentrations as an inhibitor of protein hydrolysis within digestive vacuoles was, therefore, most likely due principally to an inhibition of cathepsin activity within the vacuoles. The effect of salt was probably caused by a stimulation of both intra- and extra-particulate cathepsin activities, although 0.5–1.0 M KCl appeared to protect the particles.

Neurotensin inhibition of canine intestinal motility in vivo via α-adrenoceptors

1984 ◽  
Vol 62 (4) ◽  
pp. 403-411 ◽  
Author(s):  
Y. Sakai ◽  
E. E. Daniel ◽  
J. Jury ◽  
J. E. T. Fox
Keyword(s):  
Acetylcholine Release ◽  
Contractile Activity ◽  
Inhibitory Effect ◽  
Inhibitory Effects ◽  
Maximal Inhibition ◽  
Contractile Responses ◽  
Adrenergic Antagonists ◽  
Distal Site ◽  
Stimulation Of

Neurotensin given intra-arterially in bolus doses to the canine small intestine inhibited field-stimulated, atropine-sensitive contractile responses in the duodenum (mean effective dose (ED50) = 3.2 × 10−11 mol) and in the ileum (mean ED50 = 2.1 × 10−11 mol). Norepinephrine (ED50 = 3 × 10−9 mol) also inhibited these contractile responses. Phenylephrine (ED50 = 1.3 × 10−8 mol) was one-fourth as potent as norepinephrine and clonidine (ED50 = 8 × 10−10 mol) was at least as potent as norepinephrine, while isoproterenol (up to 8 × 10−8 mol) failed to show any inhibitory effects. Phentolamine (2 mg/kg) increased significantly the ED50 of neurotensin and norepinephrine. Prazosin (2 mg/kg) increased significantly the ED50 of norepinephrine in the duodenum but had no effect on the ED50 of neurotensin. Yohimbine (2 mg/kg) increased the ED50 values of neurotensin and adrenergic agonists. Both neurotensin and norepinephrine in doses causing maximal inhibition of field-stimulated responses decreased (by 40 to 60%) contractile responses to 9 × 10−10 mol (approximately the intra-arterial ED50 dose) of acetylcholine. Reserpine pretreatment markedly diminished the inhibition of spontaneous or field-stimulated phasic contractions by distention or field stimulation of a distal site. Reserpine also diminished the ED50 for neurotensin from 1 × 10−11 to 2 × 10−11 mol (p < 0.02), but did not abolish neurotensin's inhibitory effect. Tetrodotoxin (10–15 μg, intra-arterially) increased the dose of neurotensin required to inhibit spontaneous activity in the ileum but after this toxin, as after adrenergic antagonists or reserpine, maximal inhibition could still be obtained. These results suggested that neurotensin inhibited contractile activity of canine intestine by acting on neural receptors to release norepinephrine. Norepinephrine activated primarily α2-adrenoceptors and ultimately inhibited acetylcholine release. Neurotensin also inhibited contractions by activating a second, less sensitive receptor on smooth muscle.

The Nicola Group: Late Triassic and Early Jurassic subduction-related volcanism in British Columbia

1987 ◽  
Vol 24 (12) ◽  
pp. 2521-2536 ◽  
Author(s):  
N. Mortimer
Keyword(s):  
Tectonic Setting ◽  
Early Jurassic ◽  
Late Triassic ◽  
Calc Alkaline ◽  
High Potassium ◽  
High Concentrations ◽  
Mafic Lavas ◽  
Type 3

Mafic lavas of the Nicola Group are divided into three distinct petrographic and geochemical types: type 1 lavas are strongly augite-porphyritic picrites, basalts, and andesites that belong to a high-potassium to shoshonitic rock series; type 2 lavas are augite- and plagioclase-porphyritic basalts and andesites that belong to a low-potassium calc-alkaline series; and type 3 lavas are petrographically variable tholeiitic to transitional basalts and andesites.Low concentrations of Ti, Zr, Y, and Nb and moderate to high concentrations of K, Rb, Ba, and Sr in type 1 and 2 lavas clearly indicate a subduction-related tectonic setting of eruption. Type 3 lavas show chemical affinities intermediate between modern-day island-arc and intraplate volcanics. Type 1 (shoshonitic) lavas generally lie east of and are younger than type 2 (calc-alkaline) lavas, a relationship that implies an east-dipping early Mesozoic subduction zone beneath the Nicola arc. These interpretations resolve previous uncertainties regarding the tectonic setting of eruption of the Nicola Group.Several major 205–220 Ma plutons that intrude the Nicola Group crystallized from type 1 and 2 magmas and represent the final stages of Late Triassic to Early Jurassic arc-related igneous activity in southern Quesnellia.

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