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At least 253 records · Page 14Linked to original sources
PubMed1994

Binding and metabolism of platelet-activating factor (PAF) by isolated rat type II pneumonocytes.

The specific binding of platelet-activating factor (PAF) to isolated type II pneumonocytes from rat lung has been investigated employing an intact cell preparation. The dissociation constant (Kd) for the autacoid has been determined to be 0.46 x 10(-9) M and approximately 3000 receptor sites per cell are present. In studies conducted on the metabolism of PAF in these cells, it was demonstrated that PAF is rapidly converted into 1-alkyl-2-acylglycerophosphocholine (alkyl-acyl GPC). After longer time intervals there was a substantial conversion of alkyl-acyl GPC into alkyl-acylglycerophosphoethanolamine (alkyl-acyl GPE). Both the alkyl-acyl GPC and alkyl-acyl GPE fractions were devoid of plasmalogens. The alkyl-acyl GPC fraction was further characterized and a distinct double peak could be visualized following thin-layer chromatography and the same lyso-compound was produced from both peaks following mild alkaline hydrolysis. By using appropriate standards it was concluded that the dual alkyl-acyl GPC peaks represent differences in the fatty acid present in the sn-2 position. One peak corresponds to the presence of saturated fatty acid in the sn-2 position and is probably due to the characteristic high capacity of the type II cells to produce disaturated glycerophospholipids.

Animals↗
PubMed1994

Endothelin-1 release from endothelial cells in culture is elevated both acutely and chronically by short periods of mechanical stretch.

The effects were examined of mechanical stretch on the release of endothelin-1 (ET-1) and prostacyclin (measured as 6-keto-prostaglandin (PG) F1 alpha) from cultured endothelial cells. Stretching (0.2 Hz) for 20, 60 or 360 min caused immediate (< or = 20 min) and secondary (up to 360 min) increases in ET-1 release. The secondary but not immediate release of ET-1 was prevented by actinomycin D (8 x 10(-7) M) or cycloheximide (3.6 x 10(-6) M). Neither compound affected the release of ET-1 from unstretched cells over 360 min. Stretching of the endothelial cells increased the accumulation of 6-keto-PGF1 alpha at 360 min but not at 20 min, suggesting that stretch does not produce a rapid, non-selective increase in autacoid production from endothelial cells. The intracellular amounts of ET-1 were approximately 20 times greater than those of big ET-1. Thus, endothelial cells contain stores of ET-1 that are released rapidly by stretch.

6-Ketoprostaglandin F1 alpha↗
PubMed2001

cDNA cloning and expression of a novel cytochrome p450 (cyp4f12) from human small intestine.

A cDNA encoding a novel human CYP4F enzyme (designated CYP4F12) was cloned by PCR from a human small intestine cDNA library. RT-PCR analysis demonstrated that CYP4F12 is expressed in human small intestine and liver. This cDNA contains an entire coding region of a 524-amino-acid protein that is 81.7, 78.3, and 78.2% identical to CYP4F2, CYP4F3, and CYP4F8, respectively. When expressed in Saccharomyces cerevisiae, the P450 catalyzes leukotriene B(4) omega-hydroxylation and arachidonic acid omega-hydroxylation, typical reactions of CYP4F isoforms. Their activity levels are, however, much lower than those of CYP4F2. Interestingly, CYP4F12 catalyzes the hydroxylation of the antihistamine ebastine with significantly higher catalytic activity relative to CYP4F2 (385 vs 5 pmol/min/nmol P450). These results indicate that CYP4F12 has a different profile of substrate specificity from other CYP4F isoforms, enzymes responsible for metabolizing endogenous autacoids, therefore suggesting that it may play an important role in xenobiotic biotransformation in the human small intestine.

Amino Acid Sequence↗
PubMed2001

Identification of dual cyclooxygenase-eicosanoid oxidoreductase inhibitors: NSAIDs that inhibit PG-LX reductase/LTB(4) dehydrogenase.

Eicosanoids play key roles in many physiologic and disease processes, and their regulation by nonsteroidal anti-inflammatory drugs (NSAIDs) is critical to many therapeutic approaches. These autacoids are rapidly inactivated by specific enzymes such as 15-hydroxyprostaglandin dehydrogenase (15-PGDH) and 15-oxoprostaglandin 13-reductase/leukotriene B(4) 12-hydroxydehydrogenase (PGR/LTB(4)DH) that act on main series of eicosanoids (i.e., leukotrienes, prostaglandins), and recently found to act in lipoxin inactivation. Here, a panel of NSAIDs was assessed to determine each compound's ability to inhibit eicosanoid-directed activities of either the recombinant 15-PGDH or the PG-LXR/LTB(4)DH. The recombinant 15-PGDH that acts on both prostaglandin E(2) (PGE(2)) and lipoxin A(4) (LXA(4)) was not significantly inhibited by the NSAIDs tested. In contrast, several of the widely used NSAIDs were potent inhibitors of the PG-LXR/LTB(4)DH that metabolizes 15-oxo-PGE(2), and LTB(4) as well as 15-oxo-LXA(4). Diclofenac and indomethacin each inhibited PG-LXR/LTB(4)DH-catalyzed conversion of 15-oxo-PGE(2) to 13,14-dihydro-15-oxo-PGE(2) by 70 and 95%, respectively. Also, a COX-2 inhibitor, niflumic acid, inhibited the PG-LXR/LTB(4)DH eicosanoid oxidoreductase (EOR) by 80% while other COX-2 inhibitors such as nimesulide and NS-398 did not inhibit this enzyme. These results indicate that certain clinically useful NSAIDs such as diclofenac and indomethacin, in addition to inhibiting cyclooxygenases (1 and 2), also interfere with eicosanoid degradation by blocking PG-LXR/LTB(4)DH (EOR) and are members of a new class of dual cyclooxygenase (COX)-EOR inhibitors. Moreover, they suggest that the impact of NSAIDs on PG-LXR/LTB(4)DH activities as targets in the local tissue regulation of eicosanoid-mediated processes should be taken into account.

15-Oxoprostaglandin 13-Reductase↗
PubMed1997

Effects of exogenous and endogenous nitric oxide on the contractile function of cultured chick embryo ventricular myocytes.

Nitric oxide (NO) has been shown to be a ubiquitous intercellular autacoid in the heart and, in cultured rat ventricular myocytes, to decrease the contractile responsiveness to isoproterenol (ISO). The aim of the present study was to investigate whether exogenous (sodium nitroprusside, SNP) or endogenous nitric oxide generated from L-arginine modulated the response to ISO in cultured chick embryo ventricular myocytes. SNP 1 microM or L-arginine 1 mM had no effect on baseline contractile function. Superfusion with ISO 100 nM significantly increased myocyte amplitude of shortening to 1.31 +/- 0.06 (ratio to baseline amplitude). Initial superfusion with SNP 1 microM or L-arginine 1 mM attenuated the response to ISO to 0.89 +/- 0.05 and 1.09 +/- 0.07 respectively (P < 0.05). Potassium ferrocyanide which is not a NO donor and D-arginine the inactive substrate of NO synthase did not attenuate the response to ISO. Myocyte cGMP content was significantly increased by incubation with SNP 1 microM (31.65 +/- 3 fmol/well) but not by L-arginine 1 mM (11.1 +/- 0.3 fmol/well) as compared to myocytes incubated in control medium (11 +/- 0.9 fmol/well). Preincubation with SNP 1 microM or L-arginine 1 mM significantly attenuated the ISO mediated-increase in cAMP content from 4.33 +/- 0.2 pmol/well (ISO 100 nM alone) to 1.48 +/- 0.36 fmol/well and 1.72 +/- 0.21 pmol/well respectively. Potassium ferrocyanide and D-arginine had no effect on myocyte cGMP or cAMP content. Chick embryo myocytes have measurable and LNMMA-inhibited NO synthase activity as measured by the conversion of [3H] L-arginine to [3H] L-citrulline. In conclusion, these results demonstrate that in cultured chick embryo ventricular myocytes both exogenous and endogenous NO elevate cGMP. This may account for the inhibition of beta-adrenergic agonist-stimulated increases in cAMP and amplitude of shortening via an unidentified intracellular negative coupling.

Adrenergic beta-Agonists↗
PubMed1999

Regular slow wave flowmotion in skeletal muscle is not determined by nitric oxide and endothelin.

In a previous study we showed that the generation of regular slow wave flowmotion (rSWFM, 1-3 cycles per minute) in skeletal muscle of anesthetized rats was related to local changes of arterial pressure and microcirculatory blood flow (MBF), which suggests an involvement of pressure- or flow-induced mechanisms. The present experiments were designed to test the role of flow-dependent endothelial autacoids, such as nitric oxide (NO) and endothelin, in the generation of SWFM. The effects of NO-donor sodium nitroprusside (SNP), the partly NO-dependent metabolite adenosine (ADO), the NO-synthase inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME), and the mixed endothelin receptor blocker bosentan (BOS) were analyzed. MBF and rSWFM were assessed by laser Doppler flowmetry. rSWFM appeared in 7 out of 14 preparations after ADO (200 microg/kg/min), but not after SNP (100 microg/kg/min), L-NAME (30 mg/kg iv), and BOS (10 mg/kg iv). Its occurrence was associated with a significant decrease in arterial pressure to 50 +/- 3% (mean +/- SEM) of the baseline, provided that MBF was not enhanced. When given after induction of rSWFM by a 25% hemorrhage, SNP (50 microg/kg/min) totally abolished rSWFM and ADO (100 microg/kg/min) reduced rSWFM frequency from 2.17 +/- 0.08 to 1.72 +/- 0.08 cycles per minute (cpm) (P < 0.05), whereas the frequency was not affected by the other drugs. ADO, l-NAME (30 mg/kg iv), and BOS (10 mg/kg iv) lead to changes in rSWFM amplitude which showed a drug-independent negative correlation to changes in both MAP and MBF (R(2) = 0.61, multiple regression) in the ranges of 57-176% of MAP before drug application, and 72-120% of MBF, respectively. We conclude that NO and endothelin are not involved in the generation of rSWFM. Our findings strongly suggest that the activity of rSWFM depends on a reduction of vascular wall tension and is inhibited by SNP.

Adenosine↗
PubMedDate not supplied

Role of laryngeal afferents in cough.

The superior laryngeal nerve (SLN) is the main source of laryngeal afferent activity. A clear respiratory modulation can be noted when recording from the peripheral cut end of this nerve in several mammalian species. This modulation is due to three types of sensory endings: cold, pressure and 'drive' receptors. Although respiratory-modulated receptors play an important role in the function of the upper airway, they are not generally viewed as a primary factor in the elicitation of cough. Other more likely candidates for this role are thought to be the so-called 'irritant' endings. These are receptors that do not discharge in close association with the breathing cycle, but are usually silent or randomly active in control conditions. However, they are promptly recruited when the laryngeal mucosa is exposed to mechanical and/or chemical irritation. In fact, these receptors respond to well recognized tussigenic stimuli and are therefore thought to provide the triggering mechanisms for the cough reflex from the larynx. Endings with similar characteristics are also found in the most proximal areas of the tracheo-bronchial tree. On the basis of their response to irritants, these receptors are identified under the common denomination of 'irritant receptors'. However, within this category of endings we find a wide range of distinctive characteristics, be this in terms of responsiveness to water solutions of various osmolarity and composition or to particular responses to substances produced within the body (autacoids) or experimentally administered.

Afferent Pathways↗
PubMed1995

Regulation of IL-4 and IL-5 secretion by histamine and PGE2.

This study was designed to study the effects of autacoids on IL-4 and IL-5 secretion. IL-4 and IL-5 are secreted by TH2 cells. TH2 cells were generated by the culture of peripheral blood lymphocytes from atopic individuals in the presence of ragweed or dustmite antigen. The cloned TH2 lymphocytes were then stimulated with PMA (10 ng/ml) and alpha-CD3 (50 ng/ml) in the presence and absence of histamine (10(-4) - 10(-8)M) and PGE2 (10(-6) - 10(-8)M) for 48 hours. Other cAMP elevating agents were used as control. The supernatants were then assayed for the presence of IL-4 and IL-5 by ELISA. Both histamine and PGE2 suppressed the secretion of IL-4 in a dose dependent manner. Other cAMP elevating agents did not affect IL-4 secretion. In contrast, histamine upregulated the secretion of IL-5, whereas the effects of PGE2 on IL-5 secretion were not conclusive. Chloride channels have been implicated in the secretory processes. The effects of a chloride channel blocker, DIDS, were studied on histamine-induced suppression of IL-4 secretion. DIDS (10(-7) - 10(-12)M) abrogated the inhibitory effects of histamine on IL-4 secretion. The observations suggest that histamine may inhibit IL-4 secretion via activation of chloride channels.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1991

Histamine and its congener derivatives as immune modulators.

Our knowledge of the function of histamine as an immunoregulatory autacoid is expanding. The presence of histamine in many tissues in which the immune response takes place and its release during immune response lend credibility to the notion that histamine's role in the immune response could be an important one. In this report we present data that demonstrate the immune modulatory role of histamine. We also describe the synthesis and novel pharmacologic effects of congener derivatives of histamine. These new lymphocyte specific histamine H1 and/or H2 agonists make it feasible to assess the potential of histamine as a selective in vivo immune modulator.

Animals↗
PubMed1988

Effects of LG 30435 on different platelet activating factor-induced responses.

LG 30435 is a new potential anti-asthmatic agent with multiple sites of action. It can inhibit the bronchoconstriction induced by various agonists, including platelet activating factor (PAF). The effects of this compound on PAF-induced biological responses have now been investigated. LG 30435 inhibited both serotonin release from, and aggregation of, rabbit washed platelets evoked by PAF, being four times more potent on release than on aggregation. In contrast, it did not inhibit a number of the biological effects of PAF which are not platelet-mediated, such as contraction of guinea-pig lung parenchymal strips, hypotension in rats and lethality in mice. It may be concluded that, unless platelet PAF receptors are different from those in other tissues, LG 30435 is capable of inhibiting platelet-mediated effects of PAF by interfering with secondary mechanisms activated by this autacoid and not by direct antagonism of PAF at receptor sites.

Animals↗
PubMed1991

Endothelium-mediated regulation of coronary tone.

To what extent endothelial autacoids like endothelium-derived relaxant factor/nitric oxide (EDRF/NO), in addition to neural-humoral factors, are involved in the regulation of myocardial perfusion, is presently not known. Therefore, we investigated in conscious, chronically instrumented dogs the effect of stereospecific inhibitors (NG-monomethyl-L-arginine (L-NMMA), NG-nitro-L-arginine (L-NNA), NG-monomethylester-L-arginine (L-NAME] of nitric oxide-synthesis and -release on epicardial coronary tone (and coronary diameter) and myocardial perfusion. A hydraulic coronary cuff was used, to produce reactive hyperemia and to keep the myocardial perfusion constant over short periods. 40 mg/kg L-NNA i.v. caused a long-lasting increase in mean arterial blood pressure from 94 +/- 8 to 129 +/- 11 mmHg and a simultaneous decrease in coronary diameter by 2.8 +/- 0.3%. Heart rate dropped from 87 to 58 min-1, but the double product of heart rate and blood pressure dropped by only 8 +/- 2% (p = 0.05). The maximal coronary conductance during peak reactive hyperemia (after 20 s ischemia) indicating complete coronary dilation was diminished by 48% after L-NNA. The severe drop in resting myocardial perfusion and O2-supply, and nearly unchanged rate pressure product and thus myocardial metabolic rate following the inhibition of nitric oxide formation demonstrate a substantial contribution of EDRF/NO to the regulation of myocardial perfusion.

Acetylcholine↗
PubMed1992

Functional expression of human 5-HT1A receptors and differential coupling to second messengers in CHO cells.

The signal transduction linkages of the cloned human 5-HT1A receptor as expressed stably in CHO cells were studied. A transfected clonal cell line which expresses 900 +/- 36 fmol 5-HT1A receptor/mg protein (designated CHO-5-HT1A/WT-27) responded to 5-HT and/or 8-OH-DPAT by coupling to several second messenger pathways. The 5-HT1A receptor inhibited, but did not stimulate, membrane adenylyl cyclase activity and whole cell cAMP accumulation in a dose-dependent manner (for 5-HT, IC50 = 146 +/- 27 and 55 +/- 12 nM, respectively). Activation of the receptor was associated with other signal transduction linkages: (i) a 40-50% increase in hydrolysis of inositol phosphates (for 5-HT, EC50 = 1.33 +/- 0.15 microM for 5-HT), (ii) a transient elevation of cytosolic Ca2+ levels (apparent at 1-100 microM 5-HT) which was not affected by chelation of extracellular Ca2+ by EGTA, and (iii) an augmentation of [3H]-arachidonic acid release pharmacologically with the calcium ionophore A23187 or by activation of endogenous thrombin or P2 purinergic receptors (for 5-HT, EC50 = 1.22 +/- 0.17 microM). This pathway may be an amplification mechanism for signaling in anatomic regions with high concentrations of several neuro-transmitters, hormones or autacoids, such as at neuronal junctions or near areas of platelet aggregation. All linkages were sensitive to pertussis toxin pre-treatment (IC50 approximately 0.5-0.6 ng/ml x 4.5 h for all pathways), suggesting the involvement of Gi protein(s) in these signal transduction pathways. Coupling to varied signal transduction pathways in a single cell system may be a common feature of receptors which classically inhibit adenylyl cyclase such as the 5-HT1A receptor.

Adenylate Cyclase Toxin↗
PubMed1993

Dual action of angiotensin II on coronary resistance in the isolated perfused rabbit heart.

We studied the functional role of angiotensin II (AII) receptor subtypes and vasodilatory endothelial autacoid release in response to AII in isolated perfused rabbit hearts. AII infusion induced biphasic changes in coronary perfusion pressure (CPP): an initial increase was followed by a decrease until a plateau was reached. At higher concentrations of AII (> or = 10 nmol/l) this plateau phase was lower than the initial CPP level. AII infusion elicited inverse changes in peak left ventricular pressure (LVP): coronary constriction was associated with a transient decline, and during the plateau phase LVP was clearly increased. AII also moderately augmented prostacyclin (PGI2) release from the coronary vascular bed. The AII-induced changes in CPP, LVP, and PGI2 release were effectively inhibited by the AT1 receptor subtype antagonist ICI D8731 (30 nmol/l), but not by the AT2 receptor antagonist CGP 42112 (30 nmol/l). The adenosine A1 receptor antagonist 8-phenyltheophylline (0.1 mumol/l) attenuated the decline in CPP following the constriction phase without affecting the changes in LVP during AII infusion. The cyclooxygenase inhibitor diclofenac (1 mmol/l) had no effect on the AII-induced changes in CPP, whereas the nitric oxide-synthase inhibitor NG-nitro-L-arginine (30 mumol/l) markedly potentiated the vasoconstriction but was without effect on the plateau phase of the response. In contrast to AII, the thromboxane analogue U46619 elicited sustained increases in CPP which were associated with slight decreases in LVP.(ABSTRACT TRUNCATED AT 250 WORDS)

6-Ketoprostaglandin F1 alpha↗
PubMedDate not supplied

Paracrine functions of the coronary vascular endothelium.

Coronary vascular endothelial cells control vascular tone by modulating the local concentration of circulating vasoactive substances (e.g. adenine nucleotides, biogenic amines and bradykinin) and by synthesising and releasing the vasoactive autacoids nitric oxide (NO) and prostacyclin (PGI2). The fluid shear stress exerted by the streaming blood is the physiologically most important stimulus for a continuous endothelial NO production, which counteracts neuro- and myogenic constriction. This shear stress-dependent NO release represents a highly effective local system for maintaining adequate blood flow to the myocardial tissue. At the transcriptional level endothelium-derived NO modulates the regulation of a number of genes (e.g. monocyte chemoattractant protein-1, P-selectin and vascular cell adhesion molecule-1) most probably by direct and/or indirect interaction with transcription factors. In addition to NO and PGI2, the coronary vascular endothelium is also able to release a factor which causes hyperpolarisation of the underlying smooth muscle. This so-called endothelium-derived hyperpolarising factor (EDHF) displays the characteristics of a cytochrome P450-derived arachidonic acid metabolite. However, since NO is able to attenuate production of this factor, EDHF may contribute to the regulation of vascular tone essentially in situations associated with an apparent dysfunction of the endothelium.

Acetylcholine↗
PubMed1992

Interactions of tumor necrosis factor with local and systemic factors in fetal rat limb bones.

In many tissues the actions of tumor necrosis factor-alpha (TNF) are indirectly mediated through the production of autacoids or other cytokines. To determine the role that these factors might have in the action of TNF on bone resorption, we examined the effects of several selective inhibitors on TNF-stimulated resorption. The cyclooxygenase inhibitor indomethacin did not prevent TNF-stimulated resorption in fetal rat limb bones. Stimulation of resorption by TNF was also unaffected by the platelet activating factor antagonist WEB 2086. A 17.5 kD interleukin receptor antagonist protein, at concentrations that completely blocked the bone-resorbing actions of maximally effective concentrations of interleukin (IL)-1 beta, failed to affect the stimulatory actions of TNF. TNF-stimulated resorption was inhibited by both interferon-gamma and dexamethasone. Dexamethasone inhibited TNF-stimulated resorption more effectively than it inhibited parathyroid hormone (PTH)-stimulated resorption. When bones were treated simultaneously with low concentrations of TNF and PTH, potentiation of the bone-resorbing effects was elicited. These results suggest that TNF stimulates resorption through a pathway different from that by which PTH produces its effects. Transforming growth factor-beta (TGF-beta) enhanced responses to TNF; TGF-beta failed to inhibit the effects of TNF, even in long-term culture or when bones were pretreated with TGF-beta. Synergistic interactions between TNF and several other bone-resorbing factors have now been demonstrated. In contrast to the actions of TNF on certain other functions, the bone-resorbing effects of TNF, as determined in the fetal rat limb bone system, do not seem to be mediated by PAF, IL-1, or prostaglandins.

Animals↗
PubMed1990

Calcium influx into endothelial cells and formation of endothelium-derived relaxing factor is controlled by the membrane potential.

We studied the role of the membrane potential in the control of the intracellular free calcium concentration ([Ca2+]i) and release of the two autacoids endothelium-derived relaxing factor (EDRF = nitric oxide) and prostaglandin I2 in endothelial cells. ATP (3 mumol/l) and bradykinin (1 nmol/l) evoked rapid increases (sixfold) in [Ca2+]i in cultured endothelial cells. [Ca2+]i remained elevated over several minutes. When the cells were depolarized, either by K+ (70-90 mmol/l) or by preincubation with the blocker of K+ channels tetraethylammonium (3 mmol/l), the initial peak of [Ca2+]i remained unaffected but [Ca2+]i returned significantly faster to resting levels, indicating a reduction in Ca2+ influx. In native, freshly isolated endothelial cells, K+ abolished increases in [Ca2+]i induced by acetylcholine (3 mumol/l). Release of EDRF in response to bradykinin (cultured cells) and acetylcholine (native cells) was inhibited by K+ (by 70%), whereas release of prostaglandin I2 was not significantly reduced. Preincubation of cultured endothelial cells with the receptor-independent stimulus thimerosal (5 mumol/l, 40 min) evoked a long-lasting release of EDRF and small elevations of [Ca2+]i (twofold) after washout of the drug. Depolarization with K+ decreased thimerosal-induced EDRF release and [Ca2+]i in a reversible manner. In patch-clamped endothelial cells, bradykinin (1 nmol/l) induced transient hyperpolarizations that were significantly prolonged by BRL 34915 (1 mumol/l), an activator of K+ channels. BRL 34915 also elicited increases in [Ca2+]i, particularly in thimerosal-stimulated endothelial cells. These effects were abolished by K+. We conclude that the initial rise in [Ca2+]i in response to receptor-binding agonists, caused by mobilization of Ca2+ from intracellular stores, activates K+ channels, thereby inducing hyperpolarization.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗
PubMedDate not supplied

Regulation of the slow Ca++ channels of myocardial cells.

Contraction of the heart is regulated by a number of mechanisms, such as neurotransmitters, hormones, autacoids, pH, intracellular ATP, and Ca++ ions. These actions are mediated, at least in part, by actions on the sarcolemmal slow (L-type) Ca++ channels, exerted directly or indirectly. The major mechanisms for the regulation of the slow Ca++ channels of myocardial cells includes the following. cAMP/PK-A phosphorylation stimulates the slow Ca++ channel activity, whereas cGMP/PK-G phosphorylation inhibits. DAG/PK-C phosphorylation and tyrosine kinase phosphorylation are suggested to stimulate the slow Ca++ channel activity. Intracellular application of Gs alpha protein increases the slow Ca++ currents (ICa(L)). Lowering of intracellular ATP inhibits ICa(L). Acidosis and increase in [Ca]i inhibits ICa(L). A number of changes in the Ca++ channels also occur during development and aging. Thus, it appears that the slow Ca++ channel is a complex structure, including perhaps several associated regulatory proteins, which can be regulated by a number of extrinsic and intrinsic factors, and thereby control can be exercised over the force of contraction of the heart.

Animals↗
PubMed1980

Shigella endotoxin-induced ocular inflammation in the normal and sensory denervated rabbit eye.

Injection of Shigella endotoxin (2 mug) into the vitreous chamber of a normal rabbit eye induces on infiltration of polymorphonuclear leucocytes, miosis, a moderately intense dilation of iris, conjunctival and limbal vessels, and a breakdown in the blood-aqueous and blood-vitreal barriers. Significant amounts of soluble blood protein and prostaglandin-like (PG) material are found in the aqueous and vitreous humours withdrawn at 24 h. Endotoxin injected into the sensory denervated eye elicits similar vascular changes which appear to occur less rapidly than in normal eyes. conversely, the levels of aqueous and vireal PG-like material, as well as the capacity of excised irides to form PG from exogenous precursors, seems greater in the denervated eyes. If PG is an important mediator of ocular changes in the early phases, the results suggest that the action of this inflammatory autacoid in facilitating the ocular changes is less effective in eyes deprived of functional sensory nerves.

Animals↗