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PubMed2002

Protective effect of silymarin in antigen challenge- and histamine-induced bronchoconstriction in in vivo guinea-pigs.

The effects of silymarin on bronchoconstriction induced by antigen challenge and on post-antigen challenge hyperresponsiveness to substance P were evaluated in sensitized guinea-pigs. Silymarin significantly decreased the bronchoconstriction due to antigen administration in the early phase of the response. In contrast, the dose-response curve for substance P recorded 1 h after antigen challenge was not modified by pretreatment with silymarin. The influence of the flavonoid on hyperresponsiveness to histamine in propranolol- and PAF (platelet-activating factor)-treated animals was also assessed. Silymarin did not affect hyperresponsiveness to histamine induced by either propranolol or PAF although it had inhibitory activity on the bronchial contractile response to the autacoid. These results suggest that silymarin has a protective effect in the early phase of allergic asthma, an effect, which may be related to a negative influence of the flavonoid on bronchial responsiveness to histamine.

Animals↗
PubMed2003

Effects of cannabinoid receptor agonists on immunologically induced histamine release from rat peritoneal mast cells.

Immunologic activation of mast cells through the cross-linking of high affinity IgE receptors results in the release of inflammatory mediators which are important in the pathogenesis of allergic reactions. Early studies investigating the effects of palmitoylethanolamide on animal models of inflammation and on rat mast cells led to the hypothesis that endogenous cannabinoids might act as local autacoids which suppressed inflammation by reducing the activation of mast cells. However, more recent studies produced contradicting results. In order to evaluate if cannabinoid receptors are present in mast cells, we studied the effects of endocannabinoids (anandamide and palmitoylethanolamide) and synthetic cannabimimetics (CP 55,940, WIN 55,212-2 and HU-210) on histamine release from rat peritoneal mast cells. When incubated with mast cells alone, only anandamide could induce significant level of histamine release at concentrations higher than 10(-6) M. When mast cells were activated with anti-IgE, the histamine release induced was not affected by anandamide, palmitoylethanolamide and CP 55,940. In contrast, both WIN 55,212-2 and HU-210 enhanced anti-IgE-induced histamine release at 10(-5) M and preincubation did not increase the potency. The histamine releasing action of anandamide and the enhancing effects of WIN 55,212-2 and HU-210 on anti-IgE-induced histamine release were not reduced by the cannabinoid receptor antagonists, AM 281 and AM 630. In conclusion, the present study does not support the hypothesis that cannabinoids suppress mast cell activation. Instead, some of the cannabinoid receptor-directed ligands tested enhanced mast cell activation. However, the high concentrations required and the failure of cannabinoid receptor antagonists to reverse such effects also question the existence of functional cannabinoid receptors in mast cells.

Adjuvants, Immunologic↗
PubMed1998

Supersensitivity to serotonin- and histamine-induced arterial contraction following ovariectomy.

The modulating role of estrogens and ovariectomy on coronary artery and thoracic aortic rings was examined in female rabbits. Three treatment groups were studied: (1) control, (2) ovariectomy, and (3) ovariectomy + 17beta-estradiol acetate (40 microg/kg per day, i.m. for 7 days). Coronary artery reactivity was studied in the isolated retrogradely perfused heart. Aortic reactivity was studied using endothelium intact and denuded aortic rings. Concentration-response curves were performed to serotonin (5-HT) and histamine. A 21-fold, a 4.7-fold, and a 5.2-fold increase in sensitivity to 5-HT-induced contraction were observed in the ovariectomy group compared to the control group for coronary artery, intact aortic, and denuded aortic preparations, respectively (P < 0.05 for each comparison). Similarly, 34-fold, 4.9-fold, and 5.0-fold increases in sensitivity to histamine-induced contraction were observed in the ovariectomy group compared to control group for coronary artery, intact aortic, and denuded aortic preparations, respectively (P < 0.05 for each comparison). 17beta-Estradiol administration reversed the supersensitivity to serotonin- and histamine-induced vascular contraction observed following ovariectomy. No differences in EC50 or maximal contraction were noted between control and ovariectomy + estrogen groups. Baseline nitric oxide release and maximal 5-HT- and histamine-induced nitric oxide release from the perfused heart were decreased (P < 0.05) in ovariectomy rabbits compared to control and ovariectomy + estrogen treatment groups. The data demonstrate that (1) reduced autacoid-induced nitrous oxide release following ovariectomy and (2) direct effects upon the vascular smooth muscle contractility, which are probably mediated by altered receptor sensitivity by ovariectomy and estrogen replacement therapy. The information obtained from this study provides additional information regarding possible beneficial actions of estrogen replacement therapy in post-menopausal women.

Acetylcholine↗
PubMed1986

Effects of intracamerally infused prostaglandins on outflow facility in cynomolgus monkey eyes with intact or retrodisplaced ciliary muscle.

Cynomolgus monkeys with intact or surgically retrodisplaced ciliary muscle received intracameral infusion of prostaglandins (PG) E1, E2, and F2 alpha in doses yielding initial anterior chamber concentrations ranging from approximately 0.2 microM to approximately 0.2 mM. The effects on total outflow facility, as determined by two-level constant pressure perfusion, within the first 40 min after PG infusion were at most sporadic and minimal, and PGF2 alpha had no effect at any of the dosages given. Thus, these autacoids seem to exert little if any acute functional effect on the conventional outflow routes in this primate species when administered intracamerally under these experimental conditions.

Animals↗
PubMed2002

Leukotriene modifiers: novel therapeutic opportunities in asthma.

Cysteinyl leukotrienes (Cys-LT) are powerful proinflammatory autacoids that cause long-lasting bronchoconstriction, plasma leakage, increased mucus production; their biological activity suggests a prominent role in the etiopathology of asthma and several Cys-LT receptor antagonists and synthetase inhibitors have been developed as new antiasthmatic drugs. Zafirlukast was discovered by a mechanism-based approach to drug discovery; early structure-activity relationship analyses of the prototype SRS-A antagonist FPL-55712, lead to the identification of an indole-containing lead compound that was more specific than FPL-55712. Modifications were made on the lipid-like tail, indole backbone and acidic head region of this lead compound, resulting in potent and selective leukotriene receptor antagonists such as ICI-198615 and 204219 (zafirlukast). On the basis of successful results in preclinical asthma models, zafirlukast was recommended for clinical development and became the first leukotriene-modifier to be approved for the treatment of asthma. Leukotriene biosynthesis inhibitors (LSI) also represent a promising approach to the treatment of asthma and may theoretically provide a broader protection than Cys-LT receptor antagonists by inhibition of the synthesis of the two major leukotrienes, the Cys-LT and the chemotactic LTB4. The LSI BAY X-1005 is the result of a broad chemistry program that identified 15-HETE as an endogenous inhibitor of leukotriene synthesis and REV 5901 as a lead prototypic quinoline-based 5-lipoxygenase (5-LO) inhibitor. Clinical studies demonstrated the effectiveness of BAY X-1005 in experimental conditions such as allergen provocation and cold-air induced asthma. However, no consistent treatment effect in the overall asthma population (mild to moderately severe asthmatics) lead to discontinuation of its development.

Animals↗
PubMed1995

Regulation of L-type calcium channels of vascular smooth muscle cells.

Vascular tone is regulated by a variety of neurotransmitters, vasoactive hormones and autacoids, and vasoactive drugs. These actions are mediated, at least in part, by actions on the membrane ion channels, exerted either directly or indirectly. In this article, we described evidence that four different protein kinase systems (PK-A, PK-G, PK-C, and Ca2+/CaM-PK) act on and modulate the L-type Ca2+ slow channels in VSM cells and other types of cells. In cardiac muscle, both cAMP/PK-A and cGMP/PK-G have opposing effects. cAMP/PK-A stimulating and cGMP/PK-G inhibiting. In VSM, both cyclic nucleotides and their related kinases act in the same direction, namely both inhibit ICa(L). In skeletal muscle, both cAMP and cGMP also act in the same direction on ICa(L), but to stimulate. Ca2+ channel phosphorylation may be an important mechanism for the cyclic nucleotide-dependent actions of some vasodilators. In cardiac muscle, in addition to the slower indirect pathway--exerted via cAMP/PK-A--there is a faster more-direct pathway for ICa(L) stimulation by the beta-adrenergic receptor. This latter pathway involves direct modulation of the channel activity by the alpha subunit of the Gs-protein (Gs alpha). The two pathways (direct and indirect) are also present in VSM cells, although the indirect pathway produces inhibition of ICa(L)). PK-C and calmodulin-PK also may play roles in regulation of the L-type Ca2+ channels in smooth muscle cells, possibly mediated by phosphorylation of some regulatory-type of protein. Thus, it appears that the L-type Ca2+ slow channel is a complex structure, including perhaps several associated regulatory proteins, which can be regulated by a number of factors intrinsic and extrinsic to the cell (Figs 9, 14).

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1998

Effects of various flow types on maternal hemodynamics during fetal bypass: is there nitric oxide release during pulsatile perfusion?

OBJECTIVE: This study investigates the role of various flow conditions on maternal hemodynamics during fetal cardiopulmonary bypass. METHODS: Normothermic fetal bypass was conducted under pulsatile, or steady flow, for a 60-minute period. Fetal lamb preparations were randomly assigned to 1 of the 3 groups: steady flow (n=7), pulsatile flow (n=7), or pulsatile blocked flow bypass (n=7), where fetuses were perfused with Nomega-nitro-L-arginine after the first 30 minutes of pulsatile flow to assess the potential role of endothelial autacoids. RESULTS: Maternal oximetry and pressures remained unchanged throughout the procedure. Under fetal pulsatile flow, maternal cardiac output increased after 20 minutes of bypass and remained significantly higher than under steady flow at minute 30 (8.8+/-0.7 L x min(-1) vs 5.9+/-0.5 L x min(-1), P=.02). Maternal cardiac output in the pulsatile group also remained higher than in both steady and pulsatile blocked flow groups, reaching respectively 8.7+/-0.9 L x min(-1) vs 5.8+/-0.4 L x min(-1) (P=.02) and 5.9+/-0.3 L min(-1) (P=.01) at minute 60. Maternal systemic vascular resistances were significantly lower under pulsatile than under steady flow after 30 minutes and until the end of bypass (respectively, 9.1+/-0.6 IU vs 12.7+/-1.1 IU, P=.02 and 8.9+/-0.5 IU vs 12.9+/-1.2 IU, P=.01). Infusion of Nomega-nitro-L-arginine was followed by an increase in systemic vascular resistances from 9.3+/-0.7 IU, similar to that of the pulsatile group, to 13.5+/-1 IU at 60 minutes, similar to that of the steady flow group. CONCLUSIONS: Maternal hemodynamic changes observed under fetal pulsatile flow are counteracted after infusion of Nomega-nitro-L-arginine, suggesting nitric oxide release from the fetoplacental unit under pulsatile fetal flow conditions.

Animals↗
PubMed1986

Is vasoactive intestinal polypeptide the principal transmitter involved in human penile erection?

Previous work from this laboratory reported on the effects of several autacoids and other agents on strips of human corpus cavernosum (cc) muscle. These investigations indicated the presence in the cc muscle of a) atropine-sensitive cholinoceptors, b) alpha- and beta-adrenoceptors and c) a non-adrenergic non-cholinergic mechanism. Several recent publications have presented evidence in support of the possibility that vasoactive intestinal polypeptide (VIP) is an important, or the chief, transmitter in human penile erection. This paper describes the actions of VIP and other compounds on the cc muscle and the effect of intracavernous injection of VIP in volunteers. Among the agents tested, VIP was the most potent relaxant of the cc muscle. This effect, which was seen at a dose as low as 0.03 nM, was suppressed by VIP antiserum. The response of the isolated penile vasculature to VIP was similar. VIP antiserum had no effect on the relaxation of the cc muscle produced by field stimulation. In five of the seven subjects given intracavernous VIP (1.0 micrograms.) some degree of penile enlargement was evident, but none had an erection. It is suggested that local release of VIP, withdrawal of the alpha-adrenoceptor mediated tonic supply to the penis and the activation of the latter's beta-adrenoceptors are all probably involved in penile erection in man.

Humans↗
PubMed2000

Intrinsic prostacyclin contributes to exudation induced by bradykinin or carrageenin: a study on the paw edema induced in IP-receptor-deficient mice.

To prove that prostaglandin I2 (PGI2) is a major prostaglandin involved in bradykinin-induced exudation, we examined carrageenin- or bradykinin-induced paw edema in prostacyclin receptor-deficient mice (IPKO). Paw volume of wild-type mice (IPWT) increased gradually 5-6 hr after the carrageenin injection in a similar manner as in ICR mice, but the swelling in IPKO mice was significantly smaller (about 60% of the IPWT volume). Indomethacin, at 10 mg/kg, suppressed the swelling of the IPWT paw to the level of the non-pretreated IPKO, which was not affected by indomethacin, confirming the previous result that PGI2 is a major prostaglandin involved in the swelling. The paw edema of IPWT and IPKO was significantly attenuated by the nonpeptide bradykinin B2-receptor antagonist FR173657, at 30 mg/kg, to the same level of swelling, indicating kinin involvement. Injection of bradykinin (1.2 nmole) into the paw caused rapid edema, which peaked around 15 min in both mice. However, the edema induced in IPKO was smaller and almost at the same level as that elicited in the indomethacin-treated IPWT, suggesting that edema induced by bradykinin includes the intrinsic effect of PGI2. Concomitant injection of carbacyclin with bradykinin caused enhancement of edema in IPWT mice but not in IPKO mice, indicating that intrinsic PGI2 could cause enhancement of bradykinin- or even carrageenin-induced edema formation. These results clearly demonstrate that bradykinin released by carrageenin may be a key mediator to induce PGI2 formation, and both autacoids work together to induce enhanced inflammatory exudation.

Animals↗
PubMed2002

Lysophosphatidic acid stimulates nuclear and cytoplasmic maturation of golden hamster immature oocytes in vitro via cumulus cells.

Lysophosphatidic acid (LPA), a member of the phospholipid autacoid family, is induced in incubated human follicular fluid by lysophospholipase D. It is well known that LPA functions as a growth factor and the hypothesis that LPA in human follicular fluid takes a part in meiosis of oocytes is quite plausible. We studied the effects of LPA on the maturation of golden hamster immature oocytes in vitro. Hamster oocytes with a germinal vesicle were cultured in Tyrode's albumin lactate pyruvate (TALP) medium with 10(-5) M LPA, 10 ng/ml epidermal growth factor (EGF), 30 ng/ml insulin-like growth factor-1, 1 ng/ml tumor growth factor-alpha or 1 ng/ml basic fibroblast growth factor. The nuclear maturation rates in the LPA and EGF groups were significantly higher than in the control group and the other growth factors did not show any stimulatory effect (LPA group; 74.3% [75/101], EGF group; 82.4% [89/108] vs. control group; 60.2% [59/98], p < 0.05, p < 0.01, respectively). When the cells of cumulus were removed, EGF and LPA did not increase the nuclear maturation rates. Cotreatment EGF and LPA did not significantly enhance the stimulatory effect observed with LPA alone on maturation in vitro. The penetration rate determined by the zona-free hamster oocyte test was significantly higher in the LPA group than in the control group (26.7% vs. 13.2%, p < 0.05) and was comparable with that of oocytes matured in vivo. In conclusion, LPA stimulates the nuclear and cytoplasmic maturation of hamster immature oocytes via cumulus cells.

Animals↗
PubMed2002

The endocrine disruptor nonylphenol preferentially blocks cyclooxygenase-1.

The anthropogenic chemicals nonylphenol, bisphenol A, phthalic acid benzyl n-butyl ester, phthalic acid di-n-butyl ester and phthalic acid di(2-ethylhexyl) ester have been shown to possess sex hormone-like activity. To explore the possible actions of these chemicals on the autacoid synthesis in the body, we investigated the effects of nonylphenol, bisphenol A, phthalic acid benzyl n-butyl ester, phthalic acid di-n-butyl ester and phthalic acid di(2-ethylhexyl) ester on the activities of cyclooxygenase-1 and -2. Bisphenol A and all three phthalic acid derivatives had no significant effect on the cyclooxygenase-1 and -2 activities up to 100 microM. On the other hand, nonylphenol exhibited a marked inhibition on the cyclooxygenase-1 activity (10-100 microM nonylphenol, 7-95% inhibition), with no detectable change in the activity of cyclooxygenase-2. The inhibition patterns for the substrate, arachidonic acid, and a cofactor, phenol, were competitive and uncompetitive, respectively. These results suggest that nonylphenol can be a selective inhibitor of cyclooxygenase-1 activity.

Animals↗
PubMed1996

Changes in glycerophospholipid profile in experimental nephrotic syndrome.

We investigated changes in the glycerophospholipids in kidney tissue and its various intracellular fractions in rats with nephrotic syndrome induced by puromycin aminonucleoside. The ethanolamine plasmalogen, 1-O-alk-1'-enyl-2-acyl-GPE (EP), was increased in kidney tissue obtained from the puromycin-treated animals. A similar increase was found in the mitochondria and endoplasmic reticulum (microsomes) of this tissue. These increases were not found in the liver. Since platelet-activating factor (PAF) is known to be produced in increased amounts in inflammatory disorders, it is suggested that the higher plasmalogen found in rat kidneys during experimental nephrotic syndrome might be derived from increased levels of this autacoid. The increase in PAF may also result in the elevation of plasma PAF-acetylhydrolase (AH) activity observed in these animals.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗
PubMedDate not supplied

Vascular endothelium: vasoactive mediators.

In most blood vessels, the endothelium generates both vasodilator and growth-stabilizing mediators under normal physiological circumstances. The vasodilator influence of the endothelium modulates the vasoconstriction induced by adrenergic nerves, bloodborne substances, and local autacoids. Nitric oxide (NO) is a major endothelium-derived vasodilator, along with prostacyclin. A third substance called endothelium-derived hyperpolarizing factors (EDHF) mediates vasodilatation in certain conduit arteries and in most resistance vessels. EDHF may be a cytochrome P-450 metabolite of arachidonic acid. NO acts mostly through an elevation of cyclic guanosine monophosphate in vascular smooth muscle, whereas prostacyclin stimulates adenylate cyclase. The mode of action of EDHF involves the activation of K+ channels. The multiplicity of the factors released by the endothelium, as well as the complexity of the interactions among these factors and those with other nonendothelial mediators, determine the extent of vasomotor control exerted locally by the endothelium.

Animals↗
PubMedDate not supplied

Cardiac endothelium and tissue growth.

In recent years, a number of peptide and nonpeptide signalling autacoids have been implicated in the regulation of cardiac myocyte growth as well as vasculogenesis and angiogenesis, and in the function of cardiac muscle following development. In this review, we first examine the evidence for a role for specific cytokines during cardiac ontogeny, including fibroblast factors, TGFbeta, neuregulins, and gp/30-mediated signalling pathways. Evidence is also reviewed for a role for local, intracardiac generation of endothelins and angiotensins in the regulation of cardiac muscle function and adaptation to physiologic stress. The role of cardiac myocytes in regulating angiogenesis in the developed heart is then reviewed briefly. Finally, the effects of the endogenous generation of nitric oxides by the inflammatory cytokine-inducible isoform of nitric oxide synthase (iNOS or NOS2) within the heart are also reviewed.

Angiotensins↗
PubMed2003

Effects of endocrine disruptors on arachidonic acid metabolism in rabbit platelets.

To explore the possible actions of endocrine disruptors on the autacoid synthesis in the body, we investigated the effects of nonylphenol (NP), bisphenol A (BPA), di-n-butyl phthalate (DBP), benzyl-n-butyl phthalate (BBP), and di-2-ethylhexyl phthalate (DEHP) on the formation of 12-lipoxygenase metabolite, 12-HETE, and cyclooxygenase metabolites, TXB(2) and 12-HHT, from exogenous arachidonic acid (AA) in rabbit platelets. NP (10-50 microM) showed strong inhibition on the formation of cyclooxygenase metabolites (TXB(2), 34-95% inhibition; 12-HHT, 13-78% inhibition) and weaker inhibition on the formation of 12-HETE (0-49% inhibition). BPA, DBP, BBP, DEHP, and 17beta-estradiol (endogenous estrogen) failed to show any effect on the formation of cyclooxygenase and 12-lipoxygenase metabolites at concentrations up to 100 microM. These results suggest that NP inhibits AA metabolism in platelets and that its effects on the cyclooxygenase pathway predominate over those exerted via the 12-lipoxygenase pathway.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed1997

Pharmacological investigation of oedema induced by venom from the wasp Polistes fuscatus.

Subplantar injection of Polistes fuscatus venom induced dose-dependent rat hindpaw oedema. The oedema was significant in the first hour and reached maximum size in the fifth hour after injection of the venom (20-600 micrograms/paw). Low doses of the venom (20-80 micrograms/paw) produced oedema which disappeared within 48 hr after injection, while at doses of 300-600 micrograms/paw, oedema was present in excess of 48 hr. Pharmacological studies suggested that P. fuscatus venom-induced oedema probably has a mechanism which is multimediated. Pretreatment of rats with a combination of cyproheptadine (5 mg/kg)-captopril (2 mg/kg)-dexamethasone (1 mg/kg) inhibited the formation of oedema (maximal swelling) produced by the venom (300 micrograms/paw) by about 79% and improved the time to recovery. Paw swellings caused by 20 and 40 micrograms/paw venom were completely eliminated by the same doses of this drug combination. The kinins, autacoids (histamine and serotonin) and lipogenase derivatives are probably involved in the venom-induced oedema.

Animals↗
PubMed1997

Temperature dependence of agonist-stimulated Ca2+ signaling in cultured endothelial cells.

In cultured endothelial cells, the temperature dependence of bradykinin-initiated Ca2+ signaling was studied using Fura-2 technique. Initially, the temperature dependence of the dissociation constant of Fura-2 for Ca2+ was investigated. Temperature-initiated changes in the apparent dissociation constant (K'D) using the ratio (F340/F380) were due to a hypsochromic shift in excitation wavelengths and changes in the effective dissociation constant of Fura-2 for Ca2+ (K"D). Equations were provided to correct the dissociation constant for Fura-2, either for using the common ratio (F340/F380) or the shift corrected ratio (F340-delta lambda/F380-delta lambda). In a simple experimental protocol, the temperature dependence of the transient increase in free intracellular Ca2+ to bradykinin (i.e. Ca2+ release, sequestration and extrusion) and Ca2+/Mn2+ entry through a Ca2+ store-operated Ca2+ entry pathway (SOCP) were determined. While the temperature dependence of intracellular Ca2+ release, sequestration and extrusion (i.e. enzymatically controlled phenomena) were found to follow the same exponential function [t = A x e(-B x T); t, reaction time; A, B, constants; T, experimental temperature in K; K = degree C + 273], Ca2+/Mn2+ entry upon ion application to pre-stimulated cells strictly followed Fick's law of diffusion [t = A x (1/T) x e(B/T); t, reaction time; A, B, constants; T, experimental temperature in K]. In contrast to the temperature dependence of bradykinin-stimulated Ca2+/Mn2+ entry, the temperature dependence of Mn2+ entry on addition of agonist did not correlate with Fick's law of diffusion, but followed the same exponential function obtained for Ca2+ release, sequestration and extrusion. In conclusion, these data suggest that activation of SOCP by autacoid is due to enzymatic mechanism(s), while Ca2+ entry through SOCP, once activated, is due to a diffusion-like phenomenon.

Animals↗
PubMed1998

Protein kinase A inhibitors reverse histamine-mediated regulation of IL-5 secretion.

Histamine and IL-5 are important autacoid mediators involved in the etiology of allergic diseases. IL-5 is the main factor of eosinophilic reactions in allergy. It has been suggested that the protein kinase A-dependent (PKA) pathway of signal transduction may play the main role in histamine-induced elevation of interleukin-5 production. This study was designed to investigate the effects of the inhibitors of regulatory and catalytic subunits of PKA on histamine-mediated elevation of IL-5 production. In our study, histamine at a concentration range of 10(-4)-10(-6) M enhanced IL-5 production in D10.G4.1 cells, a mouse Th2 helper cell line. Pretreatment of this cell line with histamine at a concentration of 10(-4) M for 6-9 h had the maximum stimulatory effects (226-420%) on IL-5 production. Other cAMP-elevating agents including forskolin and Bt2-cAMP produced similar effects. The PKA inhibitors N-[2-(methylaminoethyl]-5-isoquinoline-sulfonamide (H-8) and Rp-diastereomer of adenosine cyclic 3',5'-phosphorothioate (Rp-cAMPS) were used for the inhibition of catalytic and regulatory subunits of PKA, respectively. Pretreatment of D10.G4.1 cells with H-8 at a concentration of 10(-5) M completely prevented the effects of histamine at a concentration range of 10(-6)-10(-4) M. Rp-cAMPS at 10(-5) M also prevented histamine-induced stimulation. Neither inhibitor affected IL-5 production when tested alone. These observations suggest a role for PKA in histamine-mediated increase in IL-5 production.

Animals↗