Distribution of α-adrenergic, β-adrenergic and dopaminergic receptors in discrete hypothalamic areas of rat

Catecholamine receptor binding sites were measured in discrete hypothalamic nuclei or regions as well as in certain extrahypothalamic areas of the adult male rat. For each assay, discrete areas were microdissected from frozen tissue sections and pooled from several animals. Specific high affinity binding sites were assessed at fixed ligand concentrations for [³H]p-aminoclonidine (PAC) and [³H](2-C 2′,6′-(CH₃O)₂ phenoxyethylamino)-methylbenzodioxan (WB-4101) for α-adrenergic receptor sites, for [³H]dihydroalprenolol (DHA) for β-adrenergic receptor sites, and for [³H]2-amino-6, 7-dihydroxy-1,2,3,4-tetrahydronaphtalene (ADTN) and [³H]spiroperidol in the presence of cinanserin for dopaminergic receptor sites.Regional variations in [³H]WB-4101 binding were relatively small in magnitude, with most hypothalamic and extrahypothalamic areas possessing between 60 and 90% of the binding in frontal cortex. [³H]PAC binding showed a wider range of binding density across brain areas than did [³H]WB-4101, but, in general, variations in [³H]PAC binding paralleled those in [³H]WB-4101 binding. In hypothalamus, binding was characterized as being predominantly to α₁-receptors in the of [³H]WB-4101 and to α₂-receptors in the case of [³H]PAC. The medial hypothalamic areas exhibited a somewhat higher density of these α-adrenergic sites than did the lateral hypothalamus (perifornical hypothalamus and medial forebrain bundle). Also, the ratio of [³H]PAC to [³H]WB-4101 binding differed in different hypothalamic areas, ranging from 1.5:1 to 4:1. The median eminence was exceptional in that it contained appreciable [³H]PAC but no significant [³H]WB-4101 binding sites at the radioligand concentrations tested. Binding of [³H]DHA to β-adrenergic receptors varied over approximately a 3-fold range in the different hypothalamic areas, with binding highest in the medial forebrain bundle and the medial preoptic area, and lowest in the periventricular, dorsomedial and posterior hypothalamic nuclei, the median eminence and the zona incerta. The ratio of β-adrenergic to α-adrenergic binding sites was generally lower in the medial than in the lateral hypothalamic areas and higher in the extrahypothalamic areas examined than in the hypothalamus. With regard to [³H]spiroperidol and [³H]ADTN binding to dopaminergic sites, the striatum, nucleus accumbens and olfactory tubercle showed a greater density of [³H]spiroperidol than of [³H]ADTN sites, in contrast to the hypothalamus where [³H]ADTN binding was more predominant. Within the hypothalamus, [³H]ADTN binding was relatively uniform, while [³H]spiroperidol binding was quite high in four hypothalamic areas (lateral perifornical area, medial forebrain bundle, paraventricular and dorsomedial nuclei), intermediate in the median eminence and arcuate nucleus, and low or not detectable in all other hypothalamic areas.     

Changes in the serotonin transporter in the hippocampus of subjects with schizophrenia identified using [3H]paroxetine

Summary [³H]paroxetine binding to membrane from hippocampus, obtained at autopsy, from 24 schizophrenic and 24 non-schizophrenic subjects has been measured. The affinity of [³H]paroxetine binding to hippocampal membrane was decreased in subjects with schizophrenia (Kd=0.50 ± 0.04 vs. 0.24 ± 0.02nM; mean ± S.E.M. p < 0.001) but was not different in schizophrenic subjects who had or had not committed suicide (Kd=0.50 ± 0.07 vs. 0.50 ± 0.04nM). The density of [³H]paroxetine binding sites did not differ between the schizophrenic and non-schizophrenic subjects. For the schizophrenic subjects, there was no relationship between ante-mortem neuroleptic drug treatment and [³H]paroxetine binding to the hippocampal membrane. Finally, this study has shown that neuroleptic drug treatment of rats does not alter [³H]paroxetine binding to the hippocampal membranes. Thus, it would seem that the changes in the affinity of [³H]paroxetine binding to the hippocampus of schizophrenic subjects are not likely to be due to neuroleptic drug treatment but may be involved in the pathology of the illness.     

In vivo release of newly synthesized [H]GABA in the substantia nigra of the rat: relative contribution of GABA striato-pallido-nigral afferents and nigral GABA neurons

The release of [3H]gamma-aminobutyric acid ([3H]GABA) continuously formed from [3H]glutamine has been measured with a push-pull cannula implanted in the substantia nigra of the rat anesthetized with ketamine. Consistent with the high density of GABA terminals coming from both the striato-pallido-nigral afferents, and from GABA nigrofugal neurons, our results showed that a large amount of [3H]GABA was spontaneously released in the reticulata, about 4 times higher than in the compacta. In the absence of calcium the spontaneous [3H]GABA release was reduced (-30%), as well as the K(+)-induced release of [3H]GABA (-66%). Bicuculline (10(-4) M) did not affect the K(+)-evoked release of [3H]GABA, suggesting that autoreceptors on GABA afferent fibers are distinct from the GABAA subtype. Partial lesions of striato- and pallido-nigral GABA neurons with kainic acid (1.2 micrograms) decrease by 40% the glutamic acid decarboxylase (GAD) activity in the ipsilateral SN without decreasing the spontaneous release of [3H]GABA; even following extensive lesions with kainic acid (2.5 micrograms), GAD activity (-72%) and spontaneous [3H]GABA release (-83%) were not completely abolished. These results suggest that a non-negligible contribution of GABA nigral neurons accounts for the spontaneous GABA release measured in the substantia nigra. This is further supported by the decrease (-20%), and the increase (+40%) of [3H]GABA release produced by the local application of glycine (10(-6) M), and bicuculline (10(-4) M), which respectively, inhibits and activates the nigral neuron activity. The contribution of nigral GABA neurons to the amount of [3H]GABA release from the substantia nigra, is likely linked to their high spontaneous firing rate.     

Evidence for loss of brain [H]spiroperidol and [H]ADTN binding sites in rabbit brain with aging

[³H]Spiroperidol and [³H]2-amino-6,7-dihydroxyl-1,2,3,4,-tetrahydronaphthalene hydrochloride (ADTN) binding were measured in various central nervous system regions of 5 month and 5.5 year old rabbits. In striatum, young animals had a 38% higher number of [³H]spiroperidol binding sites and a 140% higher number of [³H]ADTN binding sites than did the older animals. In frontal cortex and anterior limbic cortex there were respectively 42% and 26% more [³H]spiroperidol binding sites in the young animals. There was no change in the binding site number or affinity for [³H]spiroperidol in retina with aging. Pharmacological characterization demonstrated that [³H]spiroperidol binds to a dopamine receptor in striatum and to a serotonin receptor in cortex.     

Chronic cocaine alters brain mu opioid receptors

The possibility that dopamine may modulate the expression of opioid receptors was investigated by determining the effects of chronic cocaine administration on the density of μ opioid receptors. Quantitative in vitro autoradiography with the highly selective μ opioid ligand [³H]DAMGO was used to measure and localize changes in μ opioid receptors in the brains of rats administered cocaine or saline three times daily for 14 days. Significant increases in [³H]DAMGO binding were measured in areas of the cingulate cortex, nucleus accumbens, caudate putamen, and basolateral amygdaloid nucleus of the cocaine-treated animals. These results demonstrate that μ opioid receptors undergo upregulation in response to chronic cocaine exposure and suggest that dopamine activity can regulate the expression of μ opioid receptors.     

Autoradiographic localization of muscarinic agonist binding sites in the rat central nervous system with (+)-cis-[H]methyldioxolane

(+)-cis-[³H]Methyldioxolane ((+)-[³H]CD), a potent muscarinic agonist, was used to label high-affinity agonist states of muscarinic receptors in thin tissue sections of the rat central nervous system. Light microscopic autoradiography of atropine-sensitive (+)-[³H]CD binding sites revealed regions of dense labeling (superior colliculus, inferior colliculus, lateral geniculate body, hypoglossal (XII) nucleus, facial (VII) nucleus, tractus diagonalis) and regions of sparse labeling (hippocampus, dentate gyrus). The inverse regional correlation between high-affinity (+)-[³H]CD states and binding sites for the muscarinic antagonists [³H]pirenzepine (r = −0.79) and (-)-[³H]quinuclidinyl benzilate (r = −0.30) underscores potentially important differences between agonist and antagonist binding to CNS tissue slices.     

Ethanol administration in vivo alters calcium ions control in rat striatum

The present paper investigates the effect of chronic ethanol treatment administered through drinking water on [3H]nitrendipine binding and 45Ca uptake in rat striatum. The calcium-independent [3H]nitrendipine binding was slightly increased in treated rats, while the calcium stimulation of the binding was reduced to one fifth of the controls. In striatal slices prepared from a similar group of ethanol-treated rats the K+-stimulated 45Ca uptake was greatly reduced. These results are the first evidence of calcium-antagonist binding-site 'plasticity' following an in vivo pharmacological manipulation correlated with a change in calcium ion transport. In addition, the effect of ethanol on calcium-entry regulation may be a mechanism important for the understanding of its neurotoxic action.     

Supporting evidence for negative modulation by protons of an ion channel associated with theN-methyl-D-aspartate receptor complex in rat brain using ligand binding techniques

The addition ofL-glutamic acid (Glu) alone, both Glu and glycine (Gly) or Glu/Gly/spermidine (SPD) was effective in potentiating[³H]5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine (MK-801) binding before equilibrium to an ion channel associated with theN-methyl-D-aspartate (NMDA) receptor complex in brain synaptic membranes extensively washed and treated with Triton X-100. The binding dependent on Glu almost linearly increased in proportion to decreasing proton concentrations at a pH range of 6.0 to 9.0 in external incubation medium, while a Gly-dependent portion of the binding increased with decreasing proton concentrations up to a pH of 7.5 with a plateau thereafter. In contrast, the SPD-dependent binding increased in proportion to decreasing proton concentrations up to a pH of 7.0 with a gradual decline thereafter. Similar profiles were also obtained with [³H]MK-801 binding at equilibrium, with an exception that significant binding of [³H]MK-801 was detected in the absence of any added agonists. The potency of SPD to potentiate [³H]MK-801 binding before equilibrium increased in proportion to decreasing proton concentrations, with those of both Glu and Gly being unchanged. In contrast, the ability of (+)MK-801 to displace [³H]MK-801 binding at equilibrium was not significantly affected by a decrement of external proton concentrations from pH 7.5 to pH 8.5 in the presence of Glu/Gly and Glu/Gly/SPD added. However, similar changes in external proton concentrations did not similarly affect binding of several radioligands for the NMDA and Gly domains on the receptor complex. Decreasing proton concentrations were effective in exponentially potentiating binding of [³H]SPD at a pH range of 6.0 to 9.0 without virtually altering [³H]D, L-α-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid binding. In addition, [³H]kainic acid binding markedly decreased with decreasing proton concentrations only in the presence of Ca²⁺ ions. These results suggest that protons negatively modulate neuronal responses mediated by the NMDA receptor ionophore complex through interference with opening mechanisms of the channel domain without disturbing association processes of the endogenous agonists with the respective recognition domains in rat brain. Moreover, possible modulation by protons of responses mediated by the kainate receptor in the presence of Ca²⁺ ions at concentrations that occur in vivo is also suggested.     

Muscarinic cholinergic receptors in the human spinal cord: differential localization of [H]pirenzepine and [H]quinuclidinylbenzilate binding sites

The localization of muscarinic cholinergic receptor subtypes was studied in the human spinal cord using in vitro labelling of cryostat sections with [³H]quinuclidinylbenzilate (QNB) and [³H]pirenzepine (PZ) followed by autoradiography. The highest densities of [³H]QNB binding were localized in laminae II (substantia gelatinosa) and IX (motor neurons); in contrast, the highest density of [³H]PZ binding was localized to lamina II where the binding density was 22—32% higher than in lamina IX. These results suggest that the M₁ and M₂ muscarinic cholinergic receptor subtypes may be differentially localized in sensory and motor regions of the human spinal cord.     

β-adrenoceptor stimulation-induced increase in the number of α2-adrenoceptors of cerebral cortical membranes in rats

Effects of pre-treatment of synaptic membranes with β-adrenoceptor agonists and cholera toxin on [³H]clonidine and [³H]yohimbine binding were examined in rat cerebral cortex. Pre-incubation of cerebral cortical membranes with isoproterenol (10 or 200 μM) or dobutamine (1, 10 or 200 μM) at 37 °C for 40 min caused a significant elevation of specific [³H]clonidine binding but treatment with salbutamol (10 or 200 μM) did not. Scatchard analysis showed that 200 μM isoproterenol treatment resulted in a significant elevation of high affinity component of [³H]clonidine binding which was significantly decreased by the addition of 10μM GTP. A significant elevation in high affinity [³H]clonidine binding was observed by treatment with 100 μg/ml cholera toxin, while a significant decrease in low affinity one was by the treatment. Specific [³H]yohimbine binding was also elevated by 10 or 200 μM isoproterenol treatment. It is suggested that stimulation of β-receptors, presumably β₁-subtype could elevate the number of agonist and antagonist binding sites in α₂-receptors in synaptic membranes by partially mediated by stimulatory and/or inhibitory GTP binding regulatory proteins.     

Two binding sites for [3H]PBR28 in human brain: implications for TSPO PET imaging of neuroinflammation

[¹¹C]PBR28, a radioligand targeting the translocator protein (TSPO), does not produce a specific binding signal in approximately 14% of healthy volunteers. This phenomenon has not been reported for [¹¹C]PK11195, another TSPO radioligand. We measured the specific binding signals with [³H]PK11195 and [³H]PBR28 in brain tissue from 22 donors. Overall, 23% of the samples did not generate a visually detectable specific autoradiographic signal with [³H]PBR28, although all samples showed [³H]PK11195 binding. There was a marked reduction in the affinity of [³H]PBR28 for TSPO in samples with no visible [³H]PBR28 autoradiographic signal (K_i=188±15.6 nmol/L), relative to those showing normal signal (K_i=3.4±0.5 nmol/L, P<0.001). Of this latter group, [³H]PBR28 bound with a two-site fit in 40% of cases, with affinities (K_i) of 4.0±2.4 nmol/L (high-affinity site) and 313±77 nmol/L (low-affinity site). There was no difference in K_d or B_max for [³H]PK11195 in samples showing no [³H]PBR28 autoradiographic signal relative to those showing normal [³H]PBR28 autoradiographic signal. [³H]PK11195 bound with a single site for all samples. The existence of three different binding patterns with PBR28 (high-affinity binding (46%), low-affinity binding (23%), and two-site binding (31%)) suggests that a reduction in [¹¹C]PBR28 binding may not be interpreted simply as a reduction in TSPO density. The functional significance of differences in binding characteristics warrants further investigation.     

Chronic fluoxetine treatment upregulates 5-HT uptake sites and 5-HT2 receptors in rat brain: An autoradiographic study

This study was undertaken to investigate the effect of chronic treatment with fluoxetine, a selective serotonin uptake inhibitor used widely in the treatment of depression, on the distribution and density of 5-HT uptake sites, 5-HT₂ receptors, and vesicular amine uptake sites in rat brain. Fluoxetine (10 mg/kg i. p.) was administered daily for 21 days. The density of 5-HT uptake sites labelled by [³H]paroxetine, 5-HT₂ receptors labelled by [³H]ketanserin in presence of tetrabenazine and vesicular amine uptake sites labelled by [³H]ketanserin in the presence of mianserin were measured by quantitative autoradiography in 22 areas of rat brain, using coronal tissue sections. Chronic administration of fluoxetine produced significant increases in the density of 5-HT uptake sites in layers of frontoparietal cortex (by 32–43%), of striate cortex (by 55%), in CA1 field of hippocampus (by 111%) and in superior colliculus (by 20%). Fluoxetine treatment also resulted in upregulation of 5-HT₂ receptors in layers of frontparietal cortex (31–38%) and in CA2-3 fields of hippocampus (by 39%). The density of tetrabenazine-sensitive vesicular amine uptake sites in the caudate-putamen was also significantly increased (by 66%). The observed alterations in 5-HT uptake site and 5-HT₂ receptor densities are likely a part of adaptive neuronal changes that occur after chronic administration of fluoxetine and may be related to the antidepressant effect of the drug. © 1993 Wiley-Liss, Inc.     

Function-specific blockage of M(1) and M(3) muscarinic acetylcholine receptors by VX and echothiophate

Certain organophosphate (OP) cholinesterase inhibitors (ChEIs) are also known to bind to the muscarinic acetylcholine receptor (mAChR). The functional consequences of such binding were investigated here using the following OP compounds: VX, echothiophate, sarin, and soman. VX (charged at physiological pH) and echothiophate (formally charged) inhibited a specific signal transduction pathway in CHO cells expressing either the M(1) or M(3) mAChR. Hence, they blocked carbamylcholine (CCh)-induced cyclic adenosine monophosphate (cAMP) synthesis (muM) and had almost no effect on CCh-induced phosphoinositide (PI) hydrolysis. These substances were inactive on forskolin-induced cAMP inhibition signaling in CHO cells expressing M(2) mAChR. In binding studies, using [(3)H]-N-methyl scopolamine ([(3)H]NMS) as the competitor ligand, the ChEIs, VX and echothiophate exhibited binding to rat cortical mAChR with K(i) values in the muM range. The non-charged compounds, sarin and soman, were inert in modulating both cAMP metabolism and PI hydrolysis in CHO cells expressing M(1), M(2), and M(3) mAChRs, and no binding was observed in presence of [(3)H]NMS. These data suggest that VX and echothiophate act as function-specific blockers via a non-classical path of antagonistic activity, implying the involvement of allosteric/ectopic-binding site in M(1) and M(3) mAChRs. The functionally selective antagonistic behavior of echothiophate and VX makes them potential tools for dissecting the interactions of the mAChR with different G proteins.     

[H] -aspartate binding sites in the normal human spinal cord and changes in motor neuron disease: a quantitative autoradiographic study

The distribution and density of glutamate transporter sites was determined in human cervical and lumbar spinal cord, by quantitative autoradiography using [³H] -aspartate. In the normal human spinal cord (n = 8) there was specific binding of [³H] -aspartate throughout the spinal grey matter, with the highest levels observed in the substantia gelatinosa and central grey matter. In the ventral horns, particularly at the L5 level, focal hot spots of binding were observed in a distribution corresponding to that of lower motor neuron somata. Comparison of motor neuron disease (MND) cases (n = 12) with normal controls showed a reduction in the density of [³H] -aspartate binding in the intermediate grey matter and the substantia gelatinosa of the lumbar cord. These changes were more marked in the amyotrophic lateral sclerosis (ALS) compared to the progressive muscular atrophy (PMA) subgroup, and may be due to loss of glutamatergic terminals of the corticospinal tract. The changes observed in the cervical cord were milder and did not reach statistical significance. No differences were found between [³H] -aspartate binding in the spinal cords of the normal controls and a neurological disease control group (n = 6), suggesting that the changes observed in MND are disease specific. These findings provide further evidence in support of a disturbance of glutamatergic neurotransmission in MND.     

Decreased density of muscarinic receptors in the superior temporal gyrusin schizophrenia

Recent studies have indicated that muscarinic receptors are involved in the pathophysiology in schizophrenia, particularly in cognitive deficits. The superior temporal gyrus (STG) is an area that has also been strongly implicated in the pathophysiology of schizophrenia. Therefore, in this study, we investigated the binding density of two muscarinic antagonists, [(3)H]pirenzepine and [(3)H]AF-DX 384, in the STG of schizophrenia patients compared with controls. A significant decrease (44% in the superficial layers and 48% in the deep layers, P<0.01) in binding density of [(3)H]pirenzepine was observed in schizophrenia patients, which suggested a reduction of muscarinic M1 and M4 receptor densities in the STG of schizophrenia patients. A tendency toward decreased [(3)H]AF-DX 384 binding density (34%, P=0.09) was also observed in schizophrenia patients compared with controls. Because of the positive correlation between [(3)H]pirenzepine and [(3)H]AF-DX 384 binding, and, insofar as both ligands have high affinities for the M4 receptor, the involvement of M4 receptor alteration is also suggested in the STG in schizophrenia. These results suggest that changes of the muscarinic receptors M1 and M4 might contribute to the STG pathology in schizophrenia.     

Increased lymphocyte beta-adrenergic receptor density in progressive multiple sclerosis is specific for the CD8+, CD28- suppressor cell.

Beta-adrenergic receptor density on T cells from healthy humans is greatest on suppressor cells (CD8+, CD28-) and the effect of catecholamines, secreted by the sympathetic nervous system, predominates on this subset. The sympathetic skin response, a measure of sympathetic nervous system function, is absent in most patients with chronic progressive multiple sclerosis (MS). We measured beta-adrenergic receptor density on suppressor cells, cytotoxic cells, and monocytes from patients with chronic progressive MS and healthy control subjects. Control receptor density on suppressor cells was 2.8 +/- 0.3 fmol/10(6) cells versus a density of 5.1 +/- 0.7 fmol/10(6) cells for patients. Cytotoxic cell (CD8+, CD28+) receptor density was 1.4 +/- 0.4 fmol/10(6) cells in control subjects and 0.9 +/- 0.3 fmol/10(6) cells in the patients. Monocytes displayed beta-adrenergic receptor densities of 2.6 +/- 0.4 fmol/10(6) cells in normal individuals and 2.7 +/- 0.4 fmol/10(6) cells in the patient group. CD8 lymphocyte beta-adrenergic receptor densities in patients with relapsing-remitting and those with stable MS were not different from control values, yet were significantly less than the values for patients with chronic progressive MS. We find that mononuclear cells from healthy control subjects and patients with chronic progressive MS proliferate in response to 200 units/ml of recombinant human interleukin-2 (IL-2) similarly. However, IL-2 treatment increased beta-adrenergic receptor density on normal mononuclear cells, but failed to increase it on mononuclear cells from patients with chronic progressive MS.(ABSTRACT TRUNCATED AT 250 WORDS)     

“Peripheral” benzodiazepine binding sites in the maudsley reactive rat: Selective decrease confined to peripheral tissues

"Peripheral" benzodiazepine binding sites (PBS) were studied in both the CNS and peripheral tissues of Maudsley reactive (MR) and Maudsley non-reactive (MNR) rats using the PBS specific ligand [3H]Ro 5-4864. A statistically significant reduction in the density of PBS was found in heart and kidney of the MR compared to the MNR. Similar reductions in the density of PBS were not observed in a number of areas of the central nervous system (including cortex, hippocampus, and hypothalamus) or other peripheral tissues, such as lung and adrenal. This selective decrease in PBS in a strain selectively bred for a high degree of "fearfulness" may be related to previous findings of a reduction in the density of PBS in the same tissues in rats subjected to uncontrollable shock. These observations suggest that PBS in heart and kidney may be altered in response to fear or anxiety.     

Rapid desensitization of presynaptic dopamine autoreceptors during exposure to exogenous dopamine

When nomifensine is employed to inhibit neuronal uptake, exposure to dopamine (DA) (0.1–0.3 μM) or apomorphine (0.01–0.1 μM) inhibited, in a concentration-dependent manner, the electrically evoked release of [³H]dopamine from slices of the rabbit caudate nucleus. Apomorphine inhibited transmitter release independently of the time of exposure to the drug (6–32 min). On the other hand, the inhibitory effect of exogenous dopamine occurred only if a short period (4–12 min) of exposure was employed. In studies on the electrically evoked release of [³H]acetylcholine in slices of the rabbit caudate nucleus there was no evidence for desensitization to apomorphine or exogenous dopamine at the level of the dopamine receptors that inhibit [³H]acetylcholine release. These results indicate that the dopamine autoreceptors modulating [³H]dopamine release in the caudate nucleus become subsensitive after a few minutes of exposure to exogenous dopamine. This effect does not occur at the level of the dopamine receptors which inhibit the release of [³H]acetylcholine.     

Sympathetic skin responses are decreased and lymphocyte beta-adrenergic receptors are increased in progressive multiple sclerosis

Immune abnormalities, including deficient CD8 lymphocyte-mediated suppression, have been implicated in the progression of multiple sclerosis (MS). The peripheral sympathetic branch of the autonomic nervous system innervates the lymphoid organs and affects immune function. Animals with an ablated sympathetic nervous system develop more severe experimental allergic encephalomyelitis than control animals and exhibit an increased density of beta-adrenergic receptors on their lymphocytes. Experimental allergic encephalomyelitis shares many features with MS. Accordingly, we investigated the psychogalvanic skin reflex in patients with rapidly progressive MS and found that 13 patients (57%) lacked this sympathetic-mediated response. The density of beta-adrenergic receptors on lymphocyte subsets was increased in progressive MS, most notably on the CD8 suppressor/cytotoxic subset. B lymphocytes had the greatest number of receptors with 12.1 +/- 1.8 fmol/10(6) cells in control subjects and 18.7 +/- 2.6 fmol/10(6) cells in patients with MS. CD8 lymphocytes possessed an intermediate number of receptors with 3.4 +/- 0.4 fmol/10(6) cells in control subjects and 9.1 +/- 1.6 fmol/10(6) cells in patients with MS. CD4 lymphocytes demonstrated the fewest receptors with 1.2 +/- 0.1 fmol/10(6) cells in control subjects and 1.8 +/- 0.4 fmol/10(6) cells in patients with MS. No differences in the affinity or function (cyclic adenosine monophosphate levels in response to 10(-5) M (-)isoproterenol) of the adrenergic receptor were found when patients with progressive MS and control subjects were compared. Autonomic abnormalities in progressive MS and the increased beta-adrenergic receptor density found on CD8 lymphocytes may be related.