Adrenergic and muscarinic receptors in the human heart.
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Animals↗
Biomedical subjects
M C Michel
Publications and source records attributed to M C Michel.
Alpha2B-adrenoceptors couple to Ca2+ increase in both endogenous and recombinant expression systems.
The ability of cloned human alpha2B-adrenoceptors heterologously expressed in Sf9 cells and endogenous alpha2B-adrenoceptors in NG 108-15 neuroblastoma x glioma cells to couple to increase of intracellular Ca2+ was studied. Ca2+ increases in NG 108-15 cells were detectable but slight, whereas those in alpha2B-adrenoceptor-expressing Sf9 cells were greater. In the latter, the maximum Ca2+ increase correlated positively, and the EC50-value of noradrenaline negatively, with the receptor expression density. The order of potency of the agonists was D-medetomidine ([D]-4-[5]-[1-(2,3-dimethylphenyl)ethyl]-1H-imidazole) > noradrenaline approximately = clonidine > oxymetazoline, with clonidine and UK14,304 (5-bromo-N-[4,5-dihydro-1H-imidazole-2-yl]-6-quinoxalinamine) being weak partial agonists. In Sf9 cells Ca2+ increases consisted of concomitant mobilization from an intracellular store and influx of extracellular Ca2+. In these cells alpha2B-adrenoceptor stimulation also increased the inositol 1,4,5-trisphosphate mass. We conclude that alpha2B-adrenoceptors can couple to intracellular Ca2+ increases which may involve prior activation of phospholipase C.
Animals↗
Synthesis and adrenergic activity of a new series of N-aryl dicyclopropyl ketone oxime ethers: SAR and stereochemical aspects.
A novel series of 31 N-aryl dicyclopropyl ketone oxime ethers were synthesized and tested for their activity at alpha- and beta-adrenergic receptors. All of the compounds showed greater affinity for beta-than for alpha1-receptor sites. Some compounds had pure antagonist effects whereas some were partial agonists. Several compounds had an antagonist effect matching that of propranolol in in vitro (binding data and pA2 values on rat heart ventricle homogenates and guinea pig spontaneously beating right and electrically driven left atrial isolated preparations, respectively) and in in vivo tests (measurement of antagonism toward isoprenaline-induced tachycardia in anesthetized rats). Furthermore, all of the compounds showed a beta1-adrenergic selectivity (beta2-affinity > 1500 nM).
Adrenergic Agonists↗
Concomitant regulation of Ca2+ mobilization and G13 expression in human erythroleukemia cells.
In human erythroleukemia (HEL) cells, stimulation of alpha2-adrenoceptors by adrenaline or neuropeptide Y Y1 receptors by neuropeptide Y, concomitantly inhibit cAMP accumulation and stimulate mobilization of Ca2+ from intracellular stores via pertussis toxin-sensitive G-proteins. Treatment of HEL cells in chemically-defined, serum-free medium with 1.25% dimethylsulfoxide (DMSO) for 4 days, increased alpha2-adrenoceptor number by 120%, while the neuropeptide Y receptor number was not significantly changed. In DMSO-treated HEL cells, Ca2+ elevations by adrenaline or neuropeptide Y were significantly reduced by 28% and 57%, respectively, while basal Ca2+ and elevations by thrombin or thapsigargin were not significantly altered. Adrenaline and neuropeptide Y-induced inhibition of forskolin-stimulated cAMP accumulation was not significantly altered upon DMSO treatment. While immunodetectable alpha-subunits of Gi2 were not significantly changed by DMSO treatment, those of Gi3 were reduced by 27%. Inactivation of pertussis toxin substrates by pertussis toxin treatment and inhibition of adrenaline or neuropeptide Y stimulated Ca2+ elevations were linearly correlated. These data are compatible with the idea that, in HEL cells, alpha2-adrenoceptors and neuropeptide Y receptors couple to inhibition of adenylyl cyclase via Gi2 while they couple to Ca2+ elevations via Gi3.
Adenosine Diphosphate Ribose↗
[Terazosin].
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Adrenergic alpha-Antagonists↗
Differential alpha1-adrenoceptor labeling by [3H]prazosin and [3H]tamsulosin.
The radioligand binding properties of [3H]prazosin and [3H]tamsulosin at alpha1-adrenoceptors of several rat tissues, human prostate and cloned rat and human alpha1-adrenoceptor subtypes were compared in Tris/EDTA buffer unless otherwise indicated. The affinity of [3H]tamsulosin at tissue and cloned alpha1A- and alpha1B-adrenoceptors was somewhat greater and smaller, respectively, than that of [3H]prazosin. In most rat tissues and at cloned rat alpha1A- and alpha1B-adrenoceptors, [3H]tamsulosin had a smaller Bmax than [3H]prazosin. Studies with rat liver showed that this was due to considerably poorer labeling of agonist low affinity sites, while both radioligands detected similar numbers of agonist high affinity sites. Statistically significant differences in the number of binding sites for both ligands were not detected in HEPES or glycylglycine buffer, as the detectable receptor number for [3H]prazosin and [3H]tamsulosin tended to be smaller and greater, respectively, in these than in Tris/EDTA buffer. Among human alpha1-adrenoceptor subtypes [3H]tamsulosin labeled fewer sites than [3H]prazosin for alpha1B- but more sites for alpha1A- and alpha1D-adrenoceptors. We conclude that [3H]prazosin and [3H]tamsulosin do not detect the same number of alpha1-adrenoceptors under a variety of conditions. This should be taken into account in the interpretation of data obtained with either radioligand.
Adrenergic alpha-Antagonists↗
Comparison of human alpha1-adrenoceptor subtype coupling to protein kinase C activation and related signalling pathways.
The coupling of human alpha1-adrenoceptor subtypes to protein kinase C (PKC) and PKC-related signalling events were investigated in rat-1 fibroblasts stably expressing alpha1A-, alpha1B- or alpha1D-adrenoceptors at densities of 1328+/-200, 5030+/-703 and 150+/-14 fmol/mg protein respectively. In functional assays the alpha1-adrenoceptor agonist phenylephrine significantly stimulated PKC (assessed as increased activity in the membrane fraction) in cells expressing alpha1A- or alpha1B- but not alpha1D-adrenoceptors. In immunoblot assays phorbol ester treatment enhanced membrane-associated immunoreactivity of PKCalpha, PKCdelta and PKCepsilon to a similar extent in all three cell lines. Stimulation of alpha1A- and alpha1B-adrenoceptors also increased immunoreactivity of PKCalpha, PKCdelta and PKCepsilon in the membrane fraction, while alpha1D-adrenoceptor stimulation yielded only very small and inconsistent alterations. Immunoreactivity of PKCzeta was not consistently affected by phorbol ester or phenylephrine in any of the cell lines. Stimulation of all three alpha1-adrenoceptors time- and concentration-dependently increased inositol phosphate formation. Maximum activation occurred with the order alpha1A approximately = alpha1B > alpha1D. Phenylephrine also concentration dependently elevated free intracellular [Ca2+] in all three cell lines with the order of efficacy alpha1A > alpha1B > alpha1D. In the presence of ethanol, phenylephrine stimulated phosphatidylethanol formation in alpha1A- and alpha1B-adrenoceptor-expressing cells time and concentration dependently but only weakly and inconsistently in alpha1D-adrenoceptor-expressing cells. The efficacy of phenylephrine (100 microM) relative to that of noradrenaline (100 microM) for stimulation of phosphatidylethanol formation was similar (> or = 75%) for all three subtypes. The alkylating agent phenoxybenzamine concentration dependently reduced alpha1A-adrenoceptor density and phenylephrine-stimulated Ca2+ elevations to levels seen with alpha1D-adrenoceptors but reductions of phenylephrine-stimulated phosphatidylethanol formation were weaker. We conclude that human alpha1A- and alpha1B-adrenoceptors expressed in rat-1 cells couple to activation of PKCalpha, PKCdelta and PKCepsilon but not PKCzeta; this may involve stimulation of phospholipases C and D and intracellular Ca2+ elevations. Activation of these pathways by alpha1D-adrenoceptors appears to be much weaker and was not detected consistently; this was not fully explained by weak partial agonism of phenylephrine at this subtype or by lower receptor densities. Overall the alpha1A-adrenoceptor may have the highest efficiency of stimulus-response coupling among human alpha1-adrenoceptor subtypes.
Adrenergic alpha-1 Receptor Antagonists↗
Muscarinic receptor subtypes in porcine detrusor: comparison with humans and regulation by bladder augmentation.
The properties of muscarinic acetylcholine receptors of porcine and human bladder detrusor were compared in radioligand binding studies using [3H]quinuclidinylbenzylate as the radioligand. The receptor affinity for the radioligand and the density of muscarinic receptors was similar in male and female pigs and in humans (Kd = 35 +/- 8 pM, Bmax = 153 +/- 30 fmol/mg protein). Atropine and subtype-selective antagonists had steep and monophasic competition curves in porcine and human detrusor with a rank order of potency of atropine >> hexahydro-sila-difenidol > or = AF-DX 116 > or = pirenzepine, indicating the presence of a homogeneous population of M2 muscarinic receptors. In female pigs bladder outflow obstruction generated by partial urethral ligation or its surgical treatment by ileum augmentation or autoaugmentation did not significantly alter expression of muscarinic receptors or of alpha2A-adrenoceptors, but the power was insufficient to exclude alterations of less than 60%. We conclude that porcine and human detrusor express muscarinic receptors of the M2 subtype; despite these qualitative similarities the use of the porcine model may be limited by large biological variance with regard to quantitative receptor expression.
Animals↗
Renal effects of neuropeptide Y.
Neuropeptide Y (NPY) is a co-transmitter of the sympathetic nervous system including the renal nerves. The kidney expresses NPY receptors, which can also be activated by peptide YY (PYY), a circulating hormone released from gastrointestinal cells. Five subtypes of NPY receptors have been cloned, among which Y1, Y2 and Y5 appear to be involved in the regulation of renal function. NPY produces potent renal vasoconstriction in vitro in isolated interlobar arteries and in the isolated perfused kidney and in vivo upon intrarenal or systemic administration via a Y1 receptor. Nevertheless glomerular filtration rate is altered only little if at all by NPY, indicating a greater effect on the vas efferens than the vas afferens. NPY can inhibit renin release via Y1-like receptors. NPY can stimulate Na+/K+ adenosine triphosphatase (Na+/K+-ATPase) in proximal tubules via Y2 receptors and can antagonize the effects of vasopressin on isolated collecting ducts. It can also act prejunctionally to inhibit noradrenaline release via Y2 receptors. Despite the profound reductions of renal blood flow, systemic NPY infusion can cause diuresis and natriuresis; this is largely independent of pressure natriuresis mechanisms and is possibly mediated by an extrarenal Y5 receptor. Studies with the converting enzyme inhibitor ramiprilat and the bradykinin receptor antagonist icatibant indicate that bradykinin mediates, at least partly, diuretic NPY effects. NPY antagonists enhance basal renal blood flow but do not alter basal diuresis or natriuresis indicating that renovascular, but not tubular, NPY receptors may be tonically activated by endogenous NPY.
Animals↗
Tamsulosin treatment of 19,365 patients with lower urinary tract symptoms: does co-morbidity alter tolerability?
PURPOSE: We compare the tolerability and blood pressure effects of 0.4 mg. tamsulosin once daily in patients with lower urinary symptoms suggestive of benign prostatic obstruction with or without concomitant disease and/or antihypertensive medication. MATERIALS AND METHODS: Data from 2 open label, observational studies (study 1, 9,507 patients treated for 4 weeks and study 2, 9,858 patients treated for 12 weeks) were analyzed for global tolerability and effects on blood pressure stratifying for co-morbidity (none, diabetes, hypertension, other cardiovascular disease) and co-medication (diuretics, beta-blockers, calcium channel blockers, angiotensin converting enzyme inhibitors). RESULTS: Overall 90 and 95% of patients in studies 1 and 2, respectively, reported good or very good tolerability. While global tolerability was slightly reduced in patients with concomitant disease or some forms of medication (p < 0.05), it was rated as good or very good by more than 90 and 95% of patients even in those groups. In control patients, that is those with neither co-morbidity nor co-medication, the tamsulosin induced blood pressure reductions were similar to those previously reported for placebo treatment but were statistically significant (p < 0.05). Mean additional blood pressure reductions in patients with concomitant disease or medication were not more than 2 mm. Hg. CONCLUSIONS: Tamsulosin is well tolerated and has marginal effects on blood pressure in the majority of patients. It largely maintains its good global tolerability and minimal blood pressure effects in patients with cardiovascular co-morbidity or diabetes, or those on co-medication with antihypertensive agents.
Adrenergic alpha-Antagonists↗
Alpha 1-adrenoceptor subtypes in the human cardiovascular and urogenital systems.
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Adrenergic alpha-Antagonists↗
Possible mechanism of the negative inotropic effect of alpha1-adrenoceptor agonists in rat isolated left atria after exposure to free radicals.
1. This study was designed to investigate the mechanism(s) of the negative inotropic effects of alpha1-adrenoceptor agonists observed in rat isolated left atria after exposure to free radicals. 2. Ouabain and calphostin C were used in contraction experiments to block the sodium pump and protein kinase C. Methoxamine-induced phospholipase C and Na+/K+ ATPase activities were measured. 3. Methoxamine (300 microM) increased contractile force by 1.6 +/- 0.2 mN in control atria but decreased contractile force in electrolysis-treated atria by 2.0 +/- 0.1 mN (P < 0.05), as determined 10 min after methoxamine addition. In contrast, the positive inotropic effects of endothelin-1 (30 nM) and isoprenaline (10 microM) were reduced from 2.6 +/- 0.3 to 1.3 +/- 0.1 mN and from 2.6 +/- 0.3 to 1.7 +/- 0.2 mN, respectively, by electrolysis treatment (P < 0.05), but not converted into a negative inotropic action. 4. In an inositol phosphate assay we observed that the stimulation of phospholipase C by methoxamine was attenuated by electrolysis when the (electrolyzed) medium from the organ bath was used, but the phospholipase C responses were restored by the use of fresh medium. However, fresh medium did not counteract the negative inotropic effect of methoxamine. Accordingly, the negative inotropic effect of methoxamine is not directly related to the impaired phospholipase C responses seen in atria subjected to electrolysis. 5. Ouabain (10 microM) and the protein kinase C inhibitor calphostin C (50 nM), completely prevented the negative inotropic effect of 300 microM methoxamine in electrolysis-treated atria. 6. Measurement of the Na+/K+ ATPase activity, revealed that in control atria, alpha1-adrenoceptor stimulation with 300 microM methoxamine, decreased the Na+/K+ ATPase activity by 14.4 +/- 7.7%. In contrast, methoxamine increased the Na+/K+ ATPase activity by 48.8 +/- 8.9% (P < 0.05) in electrolysis-treated atria. Interestingly, this increase in Na+/K+ ATPase activity was completely counteracted by calphostin C (1.4 +/- 0.1% over basal). 7. These results indicate that the negative inotropic effects of alpha1-adrenoceptor agonists, observed in rat isolated left atria exposed to free radicals, are likely to be caused by protein kinase C-mediated phosphorylation and subsequent activation of the Na+/K+ ATPase.
Adrenergic alpha-1 Receptor Agonists↗
Comparison of tamsulosin efficacy in subgroups of patients with lower urinary tract symptoms.
We have compared the results of treatment with tamsulosin (0.4 mg once daily) in subgroups of patients with lower urinary tract symptoms suggestive of benign prostatic obstruction, based on two large-scale, open-label, observational studies. Improvements of IPSS or Q(max) were largely unaffected by patient age. Patients with severe symptoms benefited at least as much from treatment as those with mild or moderate symptoms, and the majority of patients with severe symptoms were shifted to the moderate or even mild symptoms group. We conclude that tamsulosin is effective in patients of all age groups, and should be considered as an alternative to surgery even in patients with severe symptoms.
Journal Article↗
Radioreceptor assay analysis of tamsulosin and terazosin pharmacokinetics.
AIMS: A radioreceptor assay has been developed for alpha1-adrenoceptor subtypes and applied to a pharmacokinetic analysis of tamsulosin and terazosin. METHODS: Young, male, healthy volunteers received 0.4 mg tamsulosin (as Omnic modified release capsules) or 5 mg terazosin (as Flotrin tablets) in a randomized, cross-over design. Before and after 1, 3, 5, 7, 10 and 23.5 h plasma was analyzed by radioreceptor assay using cloned human alpha1A-, alpha1B- and alpha1D-adrenoceptors and specific h.p.l.c. analysis. RESULTS: Following ingestion of tamsulosin median peak plasma levels of 16 ng ml(-1) were reached after 5 h and declined to 2 ng ml(-1) at 23.5 h. The time course in the radioreceptor assay was similar, and at most time points binding to alpha1A-adrenoceptors was significantly greater than to alpha1B- and alpha1D-adrenoceptors. Following ingestion of terazosin median peak plasma levels of 91 ng ml(-1) were reached after 1 h and declined to 11 ng ml(-1) at 23.5 h. In the radioreceptor assay binding also peaked at 1 h and declined thereafter, but even after 23.5 h considerable binding activity remained detectable at all three subtypes. At most time points binding to the alpha1A- and alpha1D-adrenoceptor was significantly greater than to the alpha1B-adrenoceptor. CONCLUSIONS: We conclude that alpha1-adrenoceptor antagonist pharmacokinetics can be monitored by radioreceptor assays in a subtype-selective manner. Tamsulosin and terazosin exhibit subtype selective receptor binding ex vivo. The discordance between terazosin blood levels as determined by h.p.l.c. and radioreceptor assay at late time points indicates the possible involvement of metabolites in in vivo terazosin effects.
Administration, Oral↗
Thyroid status affects the rat cardiac beta-adrenoceptor system transiently and time-dependently.
1. The aim of this study was to investigate the time-dependency of the influence of dysthyroid states on the beta-adrenoceptor system in rat heart left ventricle. Therefore, the influence of acute and chronic hyper- and hypothyroidism on beta-adrenoceptor-induced left ventricular responses, beta-adrenoceptor density, cardiac noradrenaline tissue concentrations, Gs alpha-proteins, and basal and stimulated adenylate cyclase activities was determined. 2. Hyperthyroid rats were obtained by feeding with thyroxine (T4)-containing rat-chow for 1, 4 and 8 weeks. Hypothyroidism was induced by adding 0.05% propylthiouracil (PTU) to the drinking water. Rats of varying ages were used in order to compensate for the differences in the duration of the treatments. Rats were aged 3 and 5 months at the end of the experiments. 3. Thyroxine treatment for 4 and 8 weeks increased the cardiac sensitivity to isoprenaline, but maximal induced inotropic responses were decreased. Cardiac ventricular beta-adrenoceptor density was increased only in rats treated with T4 for 1 week. This transient effect of hyperthyroidism on cardiac beta-adrenoceptor density was not observed in older rats. The PTU treatment resulted in a stable decrease of cardiac beta-adrenoceptor density. 4. Left ventricular tissue noradrenaline concentrations were unaffected by hyperthyroidism, where a decrease was observed in hypothyroid rats. Density of Gs alpha proteins was increased in hearts from chronic hyperthyroid rats. 5. These results indicate that the increased sensitivity to beta-adrenoceptor-mediated stimulation in chronic hyperthyroidism cannot be attributed to changes in cardiac beta-adrenoceptor density, but is probably caused by an enhanced content of Gs alpha. Accordingly, in hyperthyroidism, the beta-adrenoceptor system is influenced time-dependently, whereas hypothyroidism affects the beta-adrenoceptor system independent of time.
Adenylyl Cyclases↗
Profound increase in epinephrine concentration in plasma and cardiovascular stimulation after mu-opioid receptor blockade in opioid-addicted patients during barbiturate-induced anesthesia for acute detoxification.
BACKGROUND: Acute displacement of opioids from their receptors by administration of large doses of opioid antagonists during general anesthesia is a new approach for detoxification of patients addicted to opioids. The authors tested the hypothesis that mu-opioid receptor blockade by naloxone induces cardiovascular stimulation mediated by the sympathoadrenal system. METHODS: Heart rate, cardiac index, and intravascular pressures were measured in 10 patients addicted to opioids (drug history; mean +/- SD, 71 +/- 51 months) during a program of methadone substitution (96 +/- 57 mg/day). Cardiovascular variables and concentrations of catecholamine in plasma were measured in the awake state, during methohexital-induced anesthesia (dose, 74 +/- 44 microg x kg(-1) x min(-1)) before administration of naloxone, and repeatedly during the first 3 h of mu-opioid receptor blockade. Naloxone was administered initially in an intravenous dose of 0.4 mg, followed by incremental bolus doses (0.8, 1.6, 3.2, and 6.4 mg) at 15-min intervals until a total dose of 12.4 mg had been administered within 60 min; administration was then continued by infusion (0.8 mg/h). RESULTS: Concentration of epinephrine in plasma increased 30-fold (15 +/- 9 to 458 +/- 304 pg/ml), whereas concentration of norepinephrine in plasma only increased to a minor extent (76 +/- 44 to 226 +/- 58 pg/ml, P < 0.05). Cardiac index increased by 74% (2.7 +/- 0.41 to 4.7 +/- 1.7 min(-1) x m(-2)), because of increases in heart rate (89 +/- 16 to 108 +/- 17 beats/min) and stroke volume (+44%), reaching maximum 45 min after the initial injection of naloxone. In parallel, systemic vascular resistance index decreased (-40%). Systolic arterial pressure significantly increased (113 +/- 16 to 138 +/- 16 mmHg), whereas diastolic arterial pressure did not change. CONCLUSIONS: Despite barbiturate-induced anesthesia, acute mu-opioid receptor blockade in patients addicted to opioids induces profound epinephrine release and cardiovascular stimulation. These data suggest that long-term opioid receptor stimulation changes sympathoadrenal and cardiovascular function, which is acutely unmasked by mu-opioid receptor blockade. Because of the attendant cardiovascular stimulation, acute detoxification using naloxone should be performed by trained anesthesiologists or intensivists.
Adult↗
Stimulation of alpha1A-adrenoceptors in Rat-1 cells inhibits extracellular signal-regulated kinase by activating p38 mitogen-activated protein kinase.
In Rat-1 fibroblasts, endothelin-1 and a protein kinase C-stimulating phorbol ester stimulated extracellular signal-regulated kinase (ERK), whereas phenylephrine, acting at stably transfected human alpha1A-adrenoceptors, inhibited basal and endothelin-1- and phorbol ester-stimulated ERK. On the other hand, phenylephrine stimulated p38 mitogen-activated protein kinase (MAPK). Anisomycin caused p38 activation and ERK inhibition quantitatively similar to those produced by phenylephrine. SB 203,580, an inhibitor of p38, significantly attenuated phenylephrine- and anisomycin-induced ERK inhibition. The ERK inhibition by phenylephrine was not affected by the cytosolic phospholipase A2 inhibitor arachidonyltrifluoromethyl ketone or the cyclooxygenase inhibitor indomethacin but was significantly attenuated by a combination of the phosphatase inhibitors Na3VO4 and okadaic acid. Neither SB 203,580 nor the phosphatase inhibitors significantly affected ERK inhibition by the adenylyl cyclase activator forskolin. We conclude that there is a previously unrecognized interaction between ERK and p38 MAPK, in which activation of p38 causes inhibition of ERK; this may at least partly involve MAPK phosphatases that inactivate ERK.
Animals↗
Growth factor-like action of lysophosphatidic acid on human B lymphoblasts.
Proliferation and immunoglobulin secretion of B lymphocytes are regulated by specific antigens and numerous accessory immunomodulatory factors. Lysophosphatidic acid (LPA) is a glycerophospholipid mediator that is released from activated blood platelets, attains high levels in serum, and exerts potent stimulatory effects on, e.g., neutrophils, monocytes, and T lymphocytes. LPA is also generated by a secretory, cytokine-inducible phospholipase A2 present in high concentrations in inflammatory exudates and septic states. We investigated effects of LPA on human Epstein-Barr virus-immortalized B lymphoblasts, a model for immunoglobulin-secreting B cells. Intracellular Ca2+ was determined with fura 2 and the formation of inositol 1,4, 5-trisphosphate by anion-exchange chromatography. LPA stimulated an increase in inositol 1,4,5-trisphosphate levels and induced a transient rise in intracellular free Ca2+ concentration from 105 +/- 17 to 226 +/- 21 nM. This Ca2+ signal resulted from Ca2+ mobilization and Ca2+ influx and was subject to homologous desensitization. Pertussis toxin inhibited these responses by approximately 70%. Furthermore, LPA stimulated a 27.5% increase in guanosine 5'-O-(3-thiotriphosphate) binding to permeabilized B lymphoblasts, which suggests the direct activation of pertussis toxin-sensitive G proteins by LPA. LPA stimulated a strong increase in the specific phosphorylation of the mitogen-activated protein kinase (immunoblot analysis) that was prevented by the MEK inhibitor PD-98059. Finally, LPA triggered a 2-fold increase in DNA synthesis ([3H]thymidine incorporation) and a 2-fold increase in B lymphoblast number and evoked a 20- to 50-fold increase in immunoglobulin formation. By RT-PCR we detected specific mRNA transcripts for the recently cloned human LPA receptor. Thus our data suggest that LPA behaves as a B cell growth factor.
Antibody Formation↗