GABAergic nerve terminals in rat hippocampus possess alpha 2-adrenoceptors regulating GABA release

Noradrenaline enhanced in a concentration-dependent way the basal release of endogenous GABA from superfused rat hippocampus synaptosomes. The alpha 2-adrenoceptor antagonist yohimbine prevented the releasing effect of noradrenaline while the alpha 1-adrenoceptor antagonist prazosin was ineffective. It is concluded that GABAergic nerve terminals in rat hippocampus possess adrenoceptors of the alpha 2-subtype whose activation causes enhancement of GABA release.     

Nicotinic acetylcholine receptor alpha7 and alpha4beta2 subtypes differentially control GABAergic input to CA1 neurons in rat hippocampus.

The hippocampus, a limbic brain region involved in the encoding and retrieval of memory, has a well-defined structural network assembled from excitatory principal neurons and inhibitory interneurons. Because the GABAergic interneurons form synapses onto both pyramidal neurons and interneurons, the activation of nicotinic acetylcholine receptors (nAChRs) present on certain interneurons could induce either inhibition or disinhibition in the hippocampal circuitry. To understand the role of nAChRs in controlling synaptic transmission in the hippocampus, we evaluated the magnitude of nAChR-modulated GABAergic postsynaptic currents (PSCs) in pyramidal neurons and various interneurons of the CA1 region. Using whole cell patch-clamp recording and post hoc identification of neuronal types in rat hippocampal slices, we show that brief (12-s) nAChR activation by ACh (1 mM) or choline (10 mM) enhances the frequency of GABAergic PSCs in both pyramidal neurons and CA1 interneurons. The magnitude of alpha7 nAChR-mediated GABAergic inhibition, as assessed by the net charge of choline-induced PSCs, was highest in stratum lacunosum moleculare interneurons followed by pyramidal neurons and s. radiatum interneurons. In contrast, the magnitude of alpha4beta2 nAChR-mediated GABAergic inhibition, as assessed by the difference between the net charge of PSCs induced by ACh and choline, was highest in pyramidal neurons followed by s. lacunosum moleculare and s. radiatum interneurons. The present results suggest that cholinergic cues transmitted via specific subtypes of nAChRs modify the synaptic function in the hippocampus by inducing a differential degree of GABAergic inhibition in the target neurons.     

Cellular and subcellular distributions of beta1- and beta2-adrenoceptors in the CA1 and CA3 regions of the rat hippocampus

Beta-adrenoceptors (ARs) in the hippocampus play an important role in regulating synaptic plasticity and memory consolidation. However, little is known about the distributions of beta-ARs in the hippocampus, especially in the cornu ammonis (CA)1 and CA3 regions of Sprague-Dawley rats. Here, we report that beta1- and beta2-ARs in the CA1 and CA3 regions have differential subcellular distributions. Using double immunofluorescence labeling and confocal laser scanning microscopy, we found that almost all of the neuronal nuclei positive cells express beta1- and beta2-ARs, while few glial fibrillary acidic protein positive cells express them. Interestingly, beta1-ARs are predominantly distributed in the cell membrane and cytoplasm, whereas beta2-ARs are predominantly distributed not only in the membrane and cytoplasm, but also in the nucleus. The differential subcellular distribution of beta1- and beta2-ARs may have functional significance.     

Role of alpha 1-adrenoceptors in norepinephrine-induced cardiomyopathy.

This study practically delineated the contribution of alpha-adrenoceptor activation to the pathogenesis of norepinephrine (NE) cardiomyopathy. A total of 64 adult New Zealand white rabbits were used. NE cardiomyopathy was produced in rabbits by a 90-minute intravenous infusion of norepinephrine (2 micrograms/kg/min at infusion rate 0.382 ml/min). Arterial blood pressure and heart rate were constantly monitored. Arterial blood samples were obtained at 30-minute intervals for measurements of pH, blood gases, and glucose. Alpha-adrenoceptor blocking agents, when employed, were given 15 minutes prior to the initiation of NE infusion. Two days after treatment the rabbits were killed. The hearts were examined microscopically and assigned a histologic score. Pretreatment with the alpha 1-adrenoceptor blocker prazosin at 50, 100, or 200 micrograms/kg significantly reduced NE-induced myocardial injury in a dose-related manner. In contrast, the presence of alpha 2-adrenoceptor blocker yohimbine at 2.5 or 5.0 mg/kg was ineffective in preventing the formation of myocardial lesions. These findings suggest that NE cardiomyopathy may result largely from activation of the alpha 1-adrenoceptor system in the rabbit model.     

Functional alpha 1-adrenoceptors in the rat heart during beta-receptor blockade

In absence of beta-receptor blocking agents, alpha-adrenergic inotropic effects could be demonstrated in the rat myocardium for the synthetic alpha-agonists phenylephrine and methoxamine, but not for the naturally occurring catecholamines, adrenaline and noradrenaline. Other synthetic alpha-agonists were without effects. In the presence of the beta-receptor blocking agent, propranolol or timolol, marked alpha-effects were demonstrated for adrenaline and noradrenaline in both the right and left atria and the right ventricle. The results indicate that alpha-receptors may be functionally important in the beta-blocked myocardium.     

Postjunctional alpha 1- and alpha 2-adrenoceptors mediating contraction in isolated human groin arteries and veins

By means of selective agonists and antagonists for alpha 1- and alpha 2-receptors, the alpha-receptor subtypes in human groin arteries and veins were characterized and compared. In the arteries the alpha 1-receptor blocker prazosin caused a concentration-dependent parallel displacement of the noradrenaline (NA) concentration-response (cr) curve without reduction of maximum (pA2 = 9.86); the selective alpha 2-receptor antagonist rauwolscine in the concentration 10(-8) M caused a right-ward shift of the NA cr-curve without reduction of Emax, but 10(-7) M and 10(-6) M caused little or no further shift. In the veins, the two antagonists had the opposite effects. Rauwolscine caused a concentration-dependent right-ward shift of the NA cr-curve without depression of maximum (pA2 = 9.03); prazosin 10(-9) M significantly displaced the NA cr-curve, whereas 10(-8) M and 10(-7) M caused little or no further shift. The responses to the alpha 2-receptor agonist clonidine in the arteries were too small to allow calculations of pEC50 values; in the veins contractions were elicited in all vessel segments investigated (pEC50 = 6.24). Phenylephrine, selective for alpha 1-receptors, was significantly more potent in arteries than in veins. NA was significantly more potent in veins than in arteries. It is concluded that in human groin vessels, there is a functional predominance of alpha 1-receptors in the arteries and of alpha 2-receptors in the veins.     

The role of alpha1-adrenoceptors in the clonidine-induced contraction and relaxation of rat aorta

Clonidine causes dilatation of the aorta in the presence of endothelium, while it causes contraction of the aorta in the absence of endothelium. The present study was carried out to clarify the role of alpha-1-adrenoceptors in the vascular action of clonidine. The aortic rings were suspended in Krebs-Henseleit (K-H) medium, and the effects of alpha-1- and alpha-2-adrenoceptor antagonists on the clonidine-induced contractions were measured. Moreover, the role of the phosphatidylinositol (PI) response was examined. The aortic slices were incubated in K-H medium containing, [3H]myo-inositol and clonidine. The formation of [3H]inositol monophosphate (IP1) was measured with a liquid scintillation counter. Clonidine caused contraction of the aorta in the absence of endothelium, in a dose-dependent manner. This contraction was inhibited by antagonists in the following order of the potency: prazosin > phentolamine > spiperone > urapidil = yohimbine > L-659066 > atipamezole. On the other hand, clonidine inhibited norepinephrine (NE)-induced contraction in the aorta in the absence and in the presence of endothelium. Clonidine enhanced IP1 accumulation in the aorta in the absence of endothelium, whereas it inhibited NE-induced IP1 accumulation in the aorta. The present results show that alpha-1-adrenoceptors are probably involved in the clonidine-induced contraction and relaxation of the rat aorta.     

Loss of high-affinity alpha 2-adrenoceptors in Alzheimer's disease: an autoradiographic study in frontal cortex and hippocampus.

We assessed, by quantitative autoradiography, the density of high-affinity alpha 2-adrenoceptors in hippocampus and frontal cortex sections from 18 patients dying with Alzheimer's disease (AD) in comparison with a control group of 13 matched cases. The full agonist [3H]bromoxidine (UK-14304) was used as a ligand. In AD brains, the specific binding of [3H]bromoxidine was markedly decreased both in frontal cortex, the reduction ranging from 55% on layer I (P less than 0.0005) to 40% loss on layers IV-VI (P less than 0.01), and in the hippocampus where the mean of alpha 2-receptor loss was 53% both for the CA1 (P less than 0.0005) and the dentate gyrus (P less than 0.005). This dramatic decrease in the density of functional, high-affinity alpha 2-adrenoceptors very probably reflects the neuronal loss described in locus coeruleus of AD brains. The important implications of these findings for the pharmacological treatment of AD are discussed.     

Enhancement of insulin secretion during selective blockade of alpha 1- and alpha 2-adrenoceptors in the rat: effects of somatostatin

The effects of somatostatin on plasma concentrations of insulin and glucose in the presence of the selective alpha 1-adrenoceptor blocking agent prazosin or the selective alpha 2-adrenoceptor blocking drug yohimbine were studied in vivo in anesthetized rats. Infusion of both prazosin (0.080 mg/min) and yohimbine (0.018 mg/min) increased plasma insulin levels within 10 min. Prazosin, but not yohimbine, caused a significant increment in plasma glucose concentrations during the infusion of both prazosin and yohimbine, suggesting that the inhibitory effect of somatostatin is not mediated via a direct action on alpha 1- or alpha 2-adrenoceptors. Plasma glucose concentration fell slightly during somatostatin administration. A marked increment in insulin release occurred in response to cessation of the somatostatin infusion, both during prazosin- and yohimbine-treatment. We conclude that somatostatin efficiently inhibits insulin secretion during selective alpha 1- and alpha 2-adrenoceptor blockade and, further, that the insulin off-response after somatostatin treatment is potentiated by alpha-adrenoceptor blockade. This study also indicates that blockade of alpha 1- as well as alpha 2-adrenoceptors leads to an increased insulin secretion.     

Regional heterogeneity in the distribution of neurotransmitter markers in the rat hippocampus.

A detailed neurochemical analysis of the distribution of markers for the most relevant neurotransmitter systems within the rat hippocampal formation has been performed. The hippocampi, obtained from unfrozen brains of male Sprague-Dawley rats were subdissected into tissue parts containing mainly CA1, CA3 or the dentate gyrus, respectively. Each part was further divided into ventral and dorsal halves. In these six hippocampal subregions the concentrations of noradrenaline, dopamine, serotonin, 3-methoxy-4-hydroxyphenylglycol, 5-hydroxyindoleacetic acid and the putative neurotransmitter amino acids glutamate, aspartate, GABA, glycine and taurine, and the levels of somatostatin and neuropeptide Y and the activities of choline acetyltransferase, acetylcholinesterase and glutamate decarboxylase were measured. A marked heterogeneity in the subregional distribution of markers for various neurotransmitter systems within the hippocampal formation was observed. Each neuronal marker was characterized by an individual pattern of distribution. Most of the markers showed a concentration-gradient, increasing from dorsal to ventral; only taurine was more abundant in the dorsal than in the ventral parts and no dorsoventral difference was seen for aspartate, glycine and neuropeptide Y. The highest molar ratios of total 3-methoxy-4-hydroxyphenylglycol to noradrenaline and 5-hydroxyindoleacetic acid to serotonin were found in the dorsal hippocampus. The levels of noradrenaline, GABA and glutamate decarboxylase activity were highest in the dentate gyrus and lowest in CA1. The concentrations of somatostatin were highest in CA1; those of serotonin were highest in CA3. Highest activities of choline acetyltransferase and acetylcholinesterase were found in the dentate gyrus; lowest activities were found in CA3. In CA3 the lowest values of glutamate, aspartate, taurine and somatostatin were also found. The heterogeneity in the distribution of individual neurochemical markers allows insights into possible functional differences of hippocampal subregions and provides a relevant basis for future neurochemical investigations in this brain area.     

Differential response of subtypes of 5-HT1 recognition sites in the rat hippocampus to partial denervation

[3H]5-HT uptake and [3H]5-HT binding to 5-HT1 receptor subtypes (5-HT1A and non-5-HT1A sites, having high and low affinity to spiperone, respectively) were studied in the rat hippocampus ten days after two types of electrocoagulative lesions. The lesion of supracallosal area and subtotal lesion of the septum destroy supra- and subcallosal hippocampal afferents, respectively. Both types of afferents carry serotonergic fibers to the hippocampus. A significant decrease of [3H]5-HT uptake (by about one half of the control) was observed after both lesions. [3H]5-HT binding to 5-HT1A sites, comprising ca 60% of the total number of 5-HT1 sites, remained unchanged after both lesions, while the binding to non-5-HT1A sites decreased significantly (by ca 20%) but only after the lesion of the septum. The results point to a postsynaptic localization of 5-HT1A and of the bulk of non-5-HT1A sites; the decrease of the proportion of non-5-HT1A sites after septal lesion may be due to their presynaptic localization on the subcallosal pathway and/or may reflect receptor alterations in consequence of transsynaptic events in the hippocampus caused by septal lesion. Differential response of serotonin receptor subtypes to lesions of supracallosal and septal areas may underlie the differential functional responses to those lesions.     

Long-term social isolation in the rat induces opposite changes in binding to alpha 1- and alpha 2-adrenoceptors in the brain and vas deferens

Rats isolated at the time of calcification of the incisors show, after 14-18 months of social deprivation, an increased number of alpha 1-adrenoceptors labeled with [3H]WB 4101, both in the striatum and in the vas deferens, as well as a decreased number of alpha 2-adrenoceptors labeled with [3H]-clonidine in the vas deferens. Social isolation does not, however, modify the density of [3H]clonidine binding sites in the cerebral cortex. The functional state of alpha-adrenoreceptors in the vas deferens from isolated rats appears to correlate with the binding studies since the isolated tissue is hypersensitive to the contractile effect of exogenous noradrenaline and subsensitive to the inhibitory effect of clonidine on the electrically stimulated preparation.     

Decreased responsiveness of vascular postjunctional alpha1-, alpha2-adrenoceptors and neuropeptide Y1 receptors in rats with heart failure.

Heart failure is associated with increased sympathetic nerve activity. We hypothesized that chronic sympathetic stimulation in heart failure resulted in decreased vascular sympathetic responsiveness. A pithed rat model was employed to evaluate peripheral vascular alpha-adrenoceptor and neuropeptide Y (NPY) receptor responsiveness. Heart failure was induced in Sprague-Dawley rats by coronary artery ligation. Sham operated rats (Sham) served as controls. Two months after this surgical procedure, both heart failure (n = 30) and Sham (n = 30) rats underwent standard pithing procedure. Pressor responses to preganglionic sympathetic nerve stimulation (PNS) and activation of postjunctional alpha1- and alpha2-adrenoceptors as well as Y1 receptors were studied. In response to PNS, cardiac index was similar between heart failure and sham rats (P = n.s.). Mean arterial pressure (MAP) increased in a frequency-dependent fashion after PNS in heart failure rats as well as in control rats. All the agonists used, i.e. the alpha1-adrenoceptor agonist phenylephrine, the alpha2-adrenoceptor agonists clonidine and BHT933 as well as NPY, induced dose-dependent increases in MAP in heart failure and in sham rats. However, in rats with heart failure, the response to all the agonists studied was significantly decreased and the dose response curves were shifted to the right (P < 0.01). We conclude that in vivo vascular response to postjunctional alpha1- and alpha2-adrenoceptors as well as Y1 receptors are decreased in rats with heart failure.     

Regionally specific age-dependent decline in alpha 2-adrenoceptors: an autoradiographic study in human brain.

The effect of sex, postmortem delay and aging on alpha 2-adrenoceptor binding was studied in tissue sections from several representative regions of the human brain from 21 subjects using [3H]UK-14304 as a ligand. Sex and postmortem delay did not influence the density of alpha 2-receptors. Aging resulted in clear decreases in most forebrain areas examined (n. basalis greater than basal ganglia greater than hypothalamus greater than fronto-temporal cortex greater than hippocampus greater than visual cortex), whereas alpha 2-receptors did not significantly change with age in the amygdala and several infratentorial areas. We conclude that age-related, regionally specific decreases in the density of alpha 2-receptors occur in the human brain. The implications of these findings for age-dependent noradrenergic degeneration are discussed.     

Activation of alpha1-adrenoceptors increases firing frequency through protein kinase C in pyramidal neurons of rat visual cortex

Properties of repetitive firing, including spike adaptation, are considered to play an essential role in controlling neural excitability in the central nervous system. Noradrenaline is one of major neurotranmitters that modulate repetitive firing in the cerebral cortex. Although activation of beta-adrenoceptors increases firing frequency similarly to noradrenaline, it is still controversial whether alpha(1)-adrenoceptor activation influences repetitive firing. In the present study, we examined the effects of adrenoceptor agonists on firing properties and the intracellular mechanism for alpha(1)-adrenoceptor-dependent modulation of firing in pyramidal neurons of rat cerebral cortex. In agreement with previous reports, bath application of 100microM isoproterenol, a beta-adrenoceptor agonist, increased firing frequency in response to a long intracellular depolarizing current injection. Phenylephrine (100microM), an alpha(1)-adrenoceptor agonist, also increased firing rate, which was inhibited by 100microM prazosin, an alpha1-adrenoceptor antagonist. The extent of increment in firing rate is comparable to that induced by isoproterenol. Furthermore, phenylephrine's effects on firing properties were mimicked by 2-5microM phorbol ester, a protein kinase C (PKC) activator, and pre-application of 10microM chelerythrine, a PKC inhibitor, prevented phenylephrine-induced facilitation of repetitive firing. These results suggest that phenylephrine has a facilitatory effect on repetitive firing through PKC activation.     

Regional and laminar density of the dopamine innervation in adult rat cerebral cortex

The topographic distribution and density of the dopamine innervation in adult rat cerebral cortex were investigated by means of a recently improved radioautographic procedure for the light microscopic visualization and counting of monoamine axonal varicosities. Dopamine terminals were specifically labeled by high-affinity uptake in whole cerebral hemisphere slices incubated for 15 min at 35 degrees C with 10(-6) M tritiated dopamine in the presence of 10(-4) M pargyline and 5 X 10(-6) M desipramine. The slices were subsequently fixed, embedded in Epon and processed for light microscope radioautography as large 4-micron-thick (whole hemisphere) or smaller, semi-thin sections (selected areas). In radioautographs of serial semi-thin sections exposed for various periods of time, the number of labeled axonal varicosities reached a plateau after 12-14 days of exposure. Counts on such sections of increasing thickness allowed to calculate a correcting factor to transform numbers obtained from 4-micron-thick sections into their equivalent for a tissue thickness of 0.5 micron from which all varicosities were detected. The number of labeled varicosities could then be expressed per mm3 of tissue after measuring their mean caliper diameter in electron microscope radioautographs. As visualized at 3 transverse levels representing most of the major cytoarchitectonic divisions of cerebral cortex, two novel aspects were recognized in the topographic distribution of dopamine terminal: (1) the presence of a dopamine innervation in layer VIb of the frontal, parietal, temporal and occipital neocortex, and (2) a significant contingent of dopamine varicosities within the deep and not only upper layers of supragenual cingulate cortex. A fair number of dopamine varicosities were also detected in the upper layers of the dorsomedial frontal area, in the retrosplenial and adjacent occipital cortex as well as in the ventral subiculum and field CAl of the hippocampus. As measured in 10 sectors representing different cortical regions, the highest density of dopamine innervation was found in the supragenual cingulate cortex (1.7 X 10(6] and particularly in its layers II and III (3.1 X 10(6)). A slightly lower density was measured in the anteromedian "prefrontal" cortex (1.0 X 10(6)). The rostrorhinal and the perirhinal cortex showed moderate dopamine innervation (3.0 and 5.5 X 10(5)) with varicosities in every layer. The piriform and the posterior entorhinal cortex were also moderately and ubiquitously innervated (2.5 and 3.0 X 10(5)).(ABSTRACT TRUNCATED AT 400 WORDS)     

Characterization of alpha 2-adrenoceptors which increase potassium conductance in rat locus coeruleus neurones

Intracellular recordings were made from locus coeruleus neurones in a slice of rat pons superfused in vitro. A single-electrode voltage-clamp amplifier was used to measure membrane currents. Superfusion of the slice with clonidine (3-100 nM) or noradrenaline (100 nM-100 microM), or brief application of noradrenaline from a pipette by a pressure pulse, caused dose-dependent membrane hyperpolarizations. Phenylephrine (10 microM) and isoprenaline (10 microM) were ineffective. The hyperpolarizations were accompanied by a decrease in neurone input resistance. The hyperpolarization evoked by pressure ejection of noradrenaline could be reversed by membrane polarization to -110 mV. Clonidine and noradrenaline caused a membrane current which was linearly related to membrane potential between -50 and -120 mV, being outward at resting levels and reversing at -110 mV. The concentration-response curves for clonidine and noradrenaline were shifted rightwards in a parallel manner by alpha 2-adrenoceptor antagonists. The antagonist KeS estimated from the degree of shift were: RX 781094 9 nM, yohimbine 14 nM, phentolamine 20 nM and piperoxane 49 nM. These experiments indicate that in locus coeruleus neurones an increase in potassium conductance results from activation of alpha 2-adrenoceptors similar to those characterized on peripheral neurones.     

Resetting of renal autoregulation in conscious dogs: angiotensin II and alpha1-adrenoceptors

It has recently been shown, that common carotid occlusion (CCO) impairs autoregulation of renal blood flow (RBF) and glomerular filtration rate (GFR). This study was designed to investigate the mechanisms by which a moderate sympathetic stimulus influences RBF and GFR autoregulation. CCO provided a moderate sympathetic stimulus, and impaired autoregulation by increasing the lower autoregulatory limit of RBF and GFR by 21–30 mmHg. Basal RBF and GFR were not affected. A low-dose intrarenal infusion of the ₁-adrenoceptor agonist methoxamine (which did not change total RBF or GFR) induced a similar shift as CCO (n=5, RBF: +31±11 mmHg, P<0.05; GFR: +24±4 mmHg, P<0.01). In another group it was shown, that a combination of CCO with an intrarenal angiotensin II (A II) blockade (saralasin) did not significantly alter the response to CCO (n=7). These data suggest an ₁-adrenergic pathway for the sympathetic resetting of autoregulation. An augmented A II formation does not play a major role in mediating this effect.     

T-Type calcium channel alpha1G and alpha1H subunits in human retinoblastoma cells and their loss after differentiation

Human retinoblastoma cells are multipotent retinal precursor cells capable of differentiating into photoreceptors, neurons, and glia. The current-voltage relation of the undifferentiated cells is dominated by a transient inward current that disappears shortly after differentiation. In 20 mM Ba(2+)-containing bath solutions, the current has an activation midpoint near -25 mV and appears to be fully inactivated at -20 mV. Sr(2+) and Ca(2+) are preferred charge carriers relative to Ba(2+), and the current vanishes in the absence of these divalent cations. Cd(2+) blocks the current with an IC(50) of 160 microM, and Ni(2+) blocks in a biphasic manner with IC(50)s of 22 and 352 microM. The current is unaffected when sodium is replaced with other monovalent cations, and it is insensitive to nifedipine, omega-conotoxin GVIA, omega-agatoxin IVA, and omega-conotoxin MVIIC. RT-PCR revealed the presence of alpha 1G and alpha 1H mRNA in undifferentiated cells, but following differentiation, a striking reduction of both alpha 1G and alpha 1H mRNA was found, and this was paralleled by the loss of T-type Ca channel currents. alpha 1I subunit mRNA levels were low in undifferentiated and differentiated cells. These results suggest that T-type Ca channels could play a role in undifferentiated retinoblastoma cell physiology since alpha 1G and alpha 1H Ca channel subunit expression is reduced in cells that have differentiated and exited the cell cycle.     

脾淋巴细胞α2—肾上腺素能受体的特征和功能的实验研究

用放射配基结合法研究大鼠脾淋巴细胞α_2-肾上腺素能受体的特征。~3H-可乐定(~3H-CLO)与脾淋巴细胞的结合呈现快速(t1/2:2min)、可逆(t1/2:3—4min)、高亲和力(K_D:6.57±SD1.63nM)、可饱和性(B_(?a):72.4±SD13.4fmo1/10~?细胞)(n=6)和立体结构特异性等特征,表明脾淋巴细胞存在α_2-肾上腺素能受体。肾上腺素能受体激动剂抑制~3H-CLO结合的效能顺序是:肾上腺素>去甲肾上腺素>异丙肾上腺素,表明为α_2亚型。竞争实验资料的计算机分析提示,脾淋巴细胞α_2-肾上腺素能受体存在高、中、低三种亲和力状态,彼此相差2～3个数量级。在体外诱生抗体中,10umo1.L~(-1)可乐定显著抑制诱生的IgM量,可被10umol:L~(-1)酚妥拉明阻断,表明脾淋巴细胞α_2肾上腺素能受体激活抑制抗体应答。