Chronic Ethanol Exposure Increases 3H-GABA Release in Rat Hippocampus by Presynaptic Muscarinic Receptor Modulation

BACKGROUND: Chronic ethanol treatment (CET) for 28 weeks significantly increases electrically-stimulated 3H-GABA release from hippocampal slices. This increase in GABA release may be one of the mechanisms by which CET decreases the magnitude of long-term potentiation (LTP) in the hippocampus. The present study examined whether CET increases GABA release via an alteration in heterologous presynaptic cholinergic regulation. METHODS: Animals were treated with ethanol or sucrose diet for 28 weeks followed by either no withdrawal or a 48-hr withdrawal period. The electrically-stimulated 3H-GABA release from preloaded superfused hippocampal slices of naive and CET rats was measured. RESULTS: Carbachol increased 3H-GABA release in a concentration-dependent manner, and atropine modulated 3H-GABA release in a biphasic concentration-dependent manner. Atropine (10 microM) significantly blocked the effects of carbachol. Oxotremorine, a selective muscarinic receptor agonist, also increased 3H-GABA release. Mecamylamine, a selective nicotinic antagonist, did not modulate 3H-GABA release and did not block the effects of carbachol. The effects of these agents were also tested in rats 0 or 48 hrs after withdrawal from CET. The biphasic effects of atropine were decreased, whereas the facilitating effects of carbachol were significantly increased. There were no changes in the effects of these agents on 3H-acetylcholine release from hippocampal slices of CET rats compared to sucrose-treated rats. CONCLUSION: These results suggest that presynaptic muscarinic receptors facilitate GABA release, whereas nicotinic receptors do not play a significant role in modulating GABA release in hippocampus. CET selectively alters presynaptic muscarinic regulation of GABA release in hippocampus and may help us to further understand the mechanism underlying the disruption of LTP by CET.     

Ethanol enhances GABAergic transmission onto dopamine neurons in the ventral tegmental area of the rat

Background:  Activation of the dopaminergic (DA) neurons of the ventral tegmental area (VTA) by ethanol has been implicated in its rewarding and reinforcing effects. At most central synapses, ethanol generally increases inhibitory synaptic transmission; however, no studies have explored the effect of acute ethanol on GABAergic transmission in the VTA.
Methods:  Whole-cell patch clamp recordings of inhibitory postsynaptic currents (IPSCs) from VTA-DA neurons in midbrain slices from young rats.
Results  Acute exposure of VTA-DA neurons to ethanol (25 to 50 mM) robustly enhanced GABAergic spontaneous and miniature IPSC frequency while inducing a slight enhancement of spontaneous IPSC (sIPSC) amplitude. Ethanol (50 mM) enhanced paired-pulse depression of evoked IPSCs, further suggesting enhanced GABA release onto VTA-DA neurons. The frequency of sIPSCs was suppressed by the GABA_B agonist, baclofen (1.25 μM) and enhanced by the antagonist, SCH50911 (20 μM); however, neither appeared to modulate or occlude the effects of ethanol on sIPSC frequency.
Conclusions:  The present results indicate that ethanol increases postsynaptic GABA_A receptor sensitivity, enhances action potential-independent GABA release onto VTA-DA neurons, and that this latter effect is independent of GABA_B auto-receptor inhibition of GABA release.     

Attenuation of the Stimulant Response to Ethanol is Associated with Enhanced Ataxia for a GABAA, but not a GABAB, Receptor Agonist

Background:  The γ-aminobutyric acid (GABA) system is implicated in the neurobiological actions of ethanol, and pharmacological agents that increase the activity of this system have been proposed as potential treatments for alcohol use disorders. As ethanol has its own GABA mimetic properties, it is critical to determine the mechanism by which GABAergic drugs may reduce the response to ethanol (i.e., via an inhibition or an accentuation of the neurobiological effects of ethanol).
Methods:  In this study, we examined the ability of 3 different types of GABAergic compounds, the GABA reuptake inhibitor NO-711, the GABA_A receptor agonist muscimol, and the GABA_B receptor agonist baclofen, to attenuate the locomotor stimulant response to ethanol in FAST mice, which were selectively bred for extreme sensitivity to ethanol-induced locomotor stimulation. To determine whether these compounds produced a specific reduction in stimulation, their effects on ethanol-induced motor incoordination were also examined.
Results:  NO-711, muscimol, and baclofen were all found to potently attenuate the locomotor stimulant response to ethanol in FAST mice. However, both NO-711 and muscimol markedly increased ethanol-induced ataxia, whereas baclofen did not accentuate this response.
Conclusions:  These results suggest that pharmacological agents that increase extracellular concentrations of GABA and GABA_A receptor activity may attenuate the stimulant effects of ethanol by accentuating its intoxicating and sedative properties. However, selective activation of the GABA_B receptor appears to produce a specific attenuation of ethanol-induced stimulation, suggesting that GABA_B receptor agonists may hold greater promise as potential pharmacotherapies for alcohol use disorders.     

Serotonin2C Receptors and Serotonin2C Receptor-Mediated Phosphoinositide Hydrolysis in the Brain of Alcohol-Preferring and Alcohol-Nonpreferring Rats

To examine the role of serotonin_2C (5HT_2C) receptors in alcohol drinking behavior, the binding indices of 5HT_2C receptors were determined in various brain regions of alcohol-preferring (P) and alcohol-nonpreferring (NP) rats. 5HT_2C receptor-mediated phosphoinositide hydrolysis in the choroid plexus of P and NP rats was also determined. It was observed that the densities of 5HT_2C receptors are significantly higher in the hippocampus, the amygdala, and the choroid plexus, but not in the cortex of P rats compared with NP rats. The K _d values of [³H]mesulergine binding to 5HT_2C receptors were not different in these brain regions of P rats compared with NP rats. It was also observed that 5HT-stimulated [³H]inositol 1-phosphate formation was significantly higher in the choroid plexus of P rats compared with NP rats. The results of this study indicate that the numbers of 5HT_2C receptors are higher in the hippocampus, the amygdala, and the choroid plexus, and that 5HT_2C receptor-mediated phosphoinositide hydrolysis is more elevated in the choroid plexus of P rats compared with NP rats. Thus, it seems from these results that increased 5HT_2C receptors may be involved in the genetic vulnerability to alcohol drinking behavior.     

Release and Accumulation of Neurotransmitters in the Rat Brain: Acute Effects of Ethanol In Vitro and Effects of Long-Term Voluntary Ethanol Intake

Release from and accumulation in tissue slices of some neurotransmitters under acute ethanol in naive rats and in long-term voluntarily ethanol drinking rats were investigated. Slices of the rat caudatoputamen were prelabeled with [³H]choline and release of [³H]acetylcholine was stimulated through either N -methyl- d -aspartate (NMDA) receptors or strychnine-sensitive glycine receptors. Ethanol in vitro at 2%, 4%, and 6% (34 mM, 68 mM, and 102 mM, respectively) concentration-dependently depressed the maximum effect of the concentration-response curve of NMDA in naive rats. In contrast, voluntary ethanol consumption over months led to a significantly enhanced NMDA receptor response characterized by an increase in the maximum effect of the concentration-response curve. The glycine receptor-mediated release of [³H]acetylcholine, which is inhibited by acute ethanol in a competitive-like fashion, was not changed in animals that ingested ethanol over months. Electrically evoked release of [³H]noradrenaline ([³H]NA) and its presynaptic modulation by morphine through μ-opioid receptors in neocortical slices of the rat, preloaded with [³H]NA, was nearly identical in both ethanol-naive rats and in ethanol drinking rats. The accumulation of [³H]γ-aminobutyric acid in rat cerebellum tissue was neither affected by acute ethanol in vitro nor after chronic ethanol consumption. In summary, long-term voluntary ethanol intake caused a significant increase in NMDA receptor function in the rat caudatoputamen, but did not result in changes in glycine-evoked [³H]acetylcholine release of electrically evoked [³H]NA release modulated by morphine or cerebellar [³H]γ-aminobutyric acid accumulation.     

Long-Term Effects of Chronic Ethanol on Muscarinic Receptor Binding in Rat Brain

Effects of chronic ethanol treatment (CET) on muscarinic acetylcholine receptor (mAChR) binding properties were investigated via quantitative autoradiography in rats maintained on an ethanol-containing liquid diet for 28 weeks and withdrawn from ethanol for 8 weeks before harvesting of tissues. Controls received an identical diet in which sucrose was substituted isocalorically for ethanol. Maximal binding of the radiolabeled mAChR antagonist quinuclidinyl benzilate ([³H]QNB) was not reduced in hippocampal area CA1, dentate gyrus, neocortex, striatum, or thalamus, suggesting that CET results in no significant mAChR loss in these regions. Binding affinities of the cholinergic agonist carbachol to mAChRs were unaffected by CET in each of these regions, as determined by competitive displacement of [³H]QNB labeling. These results suggest that CET-induced functional deficits in brain cholinergic responses are not due to direct effects of CET on mAChR binding properties.     

Chronic myelogenous leukaemia CD34+ cells exit G0/G1 phases of cell cycle more rapidly than normal marrow CD34+ cells

To investigate the mechanisms behind the leukaemic expansion of chronic myelogenous leukaemia (CML), we examined the cell cycle status and activation kinetics of purified subpopulations of CD34⁺ cells from normal and CML bone marrow (BM). Propidium iodide staining was used to assess cell cycle status of fresh cells or those stimulated with cytokines. Although the cell cycle status of fresh low-density cells from CML and normal BM was similar, a larger percentage of CML CD34⁺ cells were cycling than those from normal BM. The HLA-DR⁻ compartment of CML CD34⁺ cells, a fraction enriched for normal, non-leukaemic progenitors, contained a higher percentage of quiescent cells than the CD34⁺ HLA-DR⁺ fraction. When the activation of CD34⁺ cells was examined in response to SCF or IL-3 alone, or SCF+IL-3+IL-6, CML CD34⁺ cells exited G₀/G₁ more rapidly than normal CD34⁺ cells. Interestingly, although normal BM CD34⁺ cells failed to cycle in response to IL-6 alone, or in the absence of exogenous cytokines, 30% of CML cells cycled under these conditions. No differences in the degree of apoptosis were documented among CML and normal CD34⁺ cells in these cultures. These data suggest that enhanced cell cycle activation of CML CD34⁺ cells, by either autocrine stimuli or via enhanced sensitivity to exogenous stimuli, may be partially responsible for the pronounced cellular expansion characteristic of CML.     

A Vitamin B12 Binder with Transcobalamin I Characteristics Synthesized and Released by Human Granulocytes in Vitro

S ummary . In-vitro synthesis and release of a vitamin-B₁₂ binding protein by peripheral leucocytes derived from healthy subjects and patients with chronic myeloid leukaemia (CML), acute promyelocytic leukaemia (APL) and acute myeloblastic leukaemia (AML) were investigated.
Myeloid cells, incubated in a nutrient medium containing [³H]leucine, incorporated labelled amino-acid into the vitamin-B₁₂ binding protein with an increase of the unsaturated vitamin-B₁₂ binding capacity (UBBC) of the cells.
The increase in the UBBC of the medium was due to the presence of the newly produced leucocyte binder which was released into the medium by the cells during incubation. On chromatography the newly synthesized binder was similar to transcobalamin I.
The incorporation of [³H]leucine into the leucocyte binder by mature granulo-cytes and undifferentiated myeloblasts was very limited and reached a maximum after 60 min of incubation. Cells from CML and APL patients showed a higher rate of incorporation of the labelled amino-acid which reached a plateau after 40 hr. The increase in the UBBC of the leucocyte binder was paralleled by the incorporation of [³H]leucine.
The percentage of immature myeloid cells in the incubation mixture (promyelocytes to stab forms) was correlated with both the incorporation of [³H]leucine and with the increase in UBBC.     

Sensitivity to Ethanol Across Development in Rats: Comparison to [3H]Zolpidem Binding

Previous research has suggested that rats tested at 28 to 30 days of age show a marked subsensitivity to the sedative effects of ethanol. In the present study, rats of different ages were tested for aerial righting following acute ethanol (3 g/kg) treatment. These results were compared with the effects of the atypical benzodiazepine zolpidem (3 and 5 mg/kg) and pentobarbital (10 and 15 mg/kg). Animals tested at 25,28, or 35 days of age were significantly less impaired by ethanol than preweanling rats (age 20 days) or older rats (age 65 to 75 days), whereas animals tested at 25 or 28 days of age were less impaired by the higher dose of zolpidem. With pentobarbital, the most distinct age-related trend was greater impairment in 20-day-old rats. Because ethanol may be active at the same type I GABA_A receptor site selectively labeled by [³H]zolpidem, levels of [³H]zolpi-dem binding were determined for rats of different ages. Although some brain regions showed progressive increases in binding of [³H]zolpidem across development, other regions demonstrated increased binding from day 12 or 17 to day, then a plateau of binding levels across days 25, and 28, with further increases occurring by day 36 or day 60. This pattern was observed in the cingulate cortex, medial septal nucleus, globus pallidus, inferior colliculus, red nucleus, and cerebellum. Overall, the results indicate that the period of subsensitivity to the sedative effects of ethanol is coincident with a change in the developmental pattern of GABA_A receptor sites targeted by [³H]zolpidem.     

Regional Differences in the Effects of Chronic Ethanol Administration on [3H]Zolpidem Binding in Rat Brain

A strong association has been observed between [³H]zolpidem binding and the presence of γ-aminobutyric acid (GABA_A) receptor mRNA for α₁-, β₂-, and γ₂-subunits in specific brain regions. This correlates with observed sensitivity of individual neurons to zolpidem and ethanol in these same regions. Previous studies using homogenate binding approaches showed small alterations in [³H] zolpidem binding levels after chronic ethanol exposure. This study was undertaken to ascertain if there is regional specificity of the effects of chronic ethanol administration on [³H] zolpidem binding levels. Chronic ethanol administration induced small, but significant alterations in [³H] zolpidem (5 nM) binding in the Inferior colliculus, substantia nigra, and the medial septum. [³H]Zolpidem binding was increased in the inferior colliculus and substantia nigra, and decreased in the medial septum. No significant differences in [³H] zolpidem binding were noted in any other brain area analyzed, including the cortex and cerebellum. These findings show that chronic ethanol administration has small effects on [³H] zolpidem binding, although they occur in a site-specific and bidirectional manner. Moreover, there is no correlation between changes in [³H] zolpidem binding and alterations In GABA_A receptor subunit expression.     

Prenatal Ethanol Exposure Diminishes Activity-Dependent Potentiation of Amino Acid Neurotransmitter Release in Adult Rat Offspring

Prenatal ethanol exposure has been associated with long-lasting intellectual impairments in children. Previous studies suggest that these deficits are, in part, linked to neurochemical abnormalities that reduce the ability to sustain long-term potentiation (LTP) in hip-pocampal formation of adult offspring. One presynaptic component of LTP that manifests during the first half-hour alter tetanic stimulation is an enhancement of amino acid neurotransmitter release. Given that the onset of enhanced neurotransmitter release correlates temporally with the decay of hippocampal LTP in prenatal ethanol-exposed offspring, we tested the hypothesis that prenatal ethanol exposure reduces tetanus stimulus-induced potentiation of electrically evoked amino acid release in hippocampal slices. Rat dams consumed 1 of 3 diets throughout gestation: (1) a BioServ liquid diet containing 5% (v/v) ethanol (26% ethanol-derived calories) that produces a maternal peak blood ethanol concentration of 83 mg/dl; (2) pair-fed an isocalorically equivalent amount of 0% ethanol liquid diet; or (3) Purina rat chow ad libitum. Hippocampal slices were prepared from adult offspring from each experimental diet group. Neither the amount of hippocampal slice tissue protein nor the incorporation of [³H]- d -aspartate (D-ASP) was affected by prenatal ethanol exposure. Furthermore, spontaneous efflux and electrically evoked D-ASP release were similar among the three diet groups. However, tetanus stimulus-induced potentiation of evoked D-ASP release in prenatal ethanol-exposed offspring was reduced to about one-third of the potentiation of D-ASP release Observed in the control diet groups. These results suggest that prenatal ethanol exposure produces long-lasting deficits in the neurochemical mechanisms responsible for activity-dependent potentiation of amino acid transmitter release without affecting the synaptic machinery responsible for amino acid uptake, storage, and release.     

Dopamine D2 Receptor Gene Expression in Rat Lines Selected for Differences in Voluntary Alcohol Consumption

A selective breeding program has led to the establishment of the alcohol-preferring AA (Alko, Alcohol) and alcohol-avoiding ANA (Alko, Nonalcohol) rat lines. To reveal putative baseline differences in dopamine receptor gene expression and dopamine receptor binding profile in the AA and ANA rat lines, we assessed striatal D₂ mRNA levels in these two rat lines. Autoradiographical studies on dopamine D₁ and D₂ receptors in the striatum and nucleus accumbens were also performed with [³H]SCH 23390 and [¹²⁵I]iodosulpiride/[³H]spiperone, respectively. The baseline differences in D₁ or D₂ receptor binding and D₂ receptor gene expression between AA and ANA rat lines are marginal, and are not likely to play a role in the genetic background of the differential alcohol drinking behavior of these rat lines.     

Inhibitory Effect of Eggs on Vitamin B12 Absorption: Description of a Simple Ovalbumin 57Co-Vitamin B12 Absorption Test

S ummary . Ovalbumin and egg yolks, mixed separately in vitro with radiocyanocobalamin (⁵⁷Co-vitamin B₁₂), were served to normal volunteers in a cooked form. Ovalbumin, and to a lesser degree, egg yolks were observed to inhibit vitamin B₁₂ absorption. This observation explains the rather poor assimilation of vitamin B₁₂ from eggs labelled in vivo with ⁵⁷Co-vitamin B₁₂.
The assimilation of vitamin B₁₂ from the ovalbumin ⁵⁷ Co-vitamin B₁₂ mixture was also measured in patients with structural alterations and functional disorders of the stomach. In contrast to the absorption test using crystalline radio-vitamin B₁₂, this simple food-vitamin B₁₂ absorption test successfully distinguished between the controls and subjects who had simple gastric achlorhydria and patients who had undergone a Billroth I or II operation or a successful vagotomy with pyloroplasty. Furthermore, this ovalbumin ⁵⁷Co-vitamin B₁₂ test successfully separated patients with pernicious anaemia from those with simple gastric achlorhydria. The ovalbumin ⁵⁷Co-vitamin B₁₂ test, in contrast to that using crystalline ⁵⁷Co-vitamin B₁₂, showed a positive correlation with the serum vitamin B₁₂ concentration. This ovalbumin⁵⁷ Co-vitamin B₁₂ test, being more physiologic and informative than the method using crystalline radio-vitamin B₁₂, is the first simple model for food-vitamin B₁₂ absorption to be proposed for research and for clinical purposes.     

Ethanol Increases GABAA Responses in Cells Stably Transfected with Receptor Subunits

Ethanol enhancement of GABA_A receptor function has been found in some, but not all, studies. These results suggest the existence of ethanol-sensitive and -resistant receptors that may differ in subunit composition, although methodological differences (e.g., ³⁸Cl^- flux versus membrane currents) could also contribute to the different results. To examine these possibilities, we used mouse L(tk^-) cells stably transfected with α₁+β or α+β₁+γ_2L GABA_A receptor subunit DNAs and compared ³⁸Cl flux with whole-cell, patch-clamp measurements of GABA_A receptor function. Both techniques detected a similar modulation of the GABA receptor by ethanol, flunitrazepam, and pentobarbital. The potentiating action of ethanol required the -γ-subunit and was maximal at a concentration of 10 m m . Similar ethanol potentiation was obtained with brief (20 msec) or long (2 sec) applications of GABA. Analysis of data obtained from individual cells expressing α₁β_1-γ_2L subunits showed considerable variability in sensitivity to ethanol, particularly with concentrations of 30 and 100 m m . Ethanol potentiated GABA action if the cells were grown on coverslips coated with polylysine, but had no effect on GABA_A receptors of cells grown on uncoated coverslips. Thus, ethanol action was influenced by the growth matrix. Taken together, these data indicate that a y-subunit is necessary, but not sufficient, for ethanol sensitivity in this cell system. We suggest that posttranslational processing, particularly receptor phosphorylation, may also be important and that stably transfected cells will be useful in elucidating these events.     

Absence of Intrinsic Factor from Human Portal Plasma during 57CoB12 Absorption in Man

S ummary The ⁵⁷CoB₁₂ activity in blood obtained from the portal vein during ⁵⁷CoB₁₂ absorption did not have the biological or the immunological features in vitro of intrinsic factor from normal human gastric juice.
This indicates that ⁵⁷CoB₁₂ probably is not absorbed from the intestine with intrinsic factor.     

A Study of 'Haemosiderin'in the Marrow of the Femur of Normal Young Adult Rabbits Compared with that in Rabbits 4 Months after an Intravenous Injection of 239Pu(NO3)4

A study of the distribution of cells containing iron, as demonstrated by Perls'reagent, in the marrow of the femur of normal young adult rabbits in comparison with that in rabbits of the same age group 4 months after an intravenous injection of ²³⁹Pu(NO₃)₄ is described.
The number of iron containing cells, which are probably macrophages, was found to be variable in the length of the bone and also from one normal rabbit to another. The amount of pigment in any one cell was also variable.
A significant increase in the number of iron containing cells and in the amount of pigment the cells contained was noted in the marrow of the femur of rabbits 4 months after a single intravenous injection of ²³⁹Pu(NO₃)₄, compared with the normal controls. ²³⁹Pu aggregates close to the mineralized surface were not characteristically associated with haemosiderin.
This work was carried out at the Medical Research Council Unit for Research on Bone-Seeking Isotopes, Oxford, while the author was holding a World Health Organization Fellowship.
I am indebted to Dr. Janet Vaughan and Mrs. Betty Bleaney for much helpful advice and discussion. I also wish to thank Dr. David Taylor, Department of Biophysics, The Royal Cancer Hospital, for injecting the rabbits with ²³⁹Pu(NO₃)₄. I appreciate the technical help of Mr. John Halfacre.     

Human GABA, Receptor αl and α3 Subunits Genes and Alcoholism

γ-Aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the brain. GABA effects are largely mediated by binding to the postsynaptic GABA_A receptor, causing the opening of an integral chloride-ion channel. The GABA_A antagonists picrotoxin and bicuculline reduce some ethanol-induced behaviors, such as motor impairment, sedation, and hypnosis. The role of this receptor in alcoholism is further supported by effective alleviation of alcohol withdrawal symptoms by GABA_A agonists. To determine the role of the GABA, receptor (GABR) genes in the development of alcoholism, we have used α₁ and α ₃ simple sequence repeat polymorphisms in a sample of unrelated alcoholics, alcoholic probands with both parents, and psychiatrically normal controls. For the GABRα₁ gene, the differences between allele frequencies, when all alleles were compared together, were not significant between total alcoholics, subtypes of alcoholics, and normal controls. However, for GABRα₃, the differences between total alcoholics and normal controls were significant when all alleles were compared together. The differences between subtypes of alcoholics and normal controls were not significant. The results of haplotype relative risk analysis for both genes, GABRα₁ and GABRα₃, were also negative. It is possible that the sample size in the haplotype relative risk is too small to have power to detect the differences in transmitted versus nontransmitted alleles. There is a need for a replication study in a large family sample, that will allow haplotype relative risk or affected sib-pair analysis.     

Structural Determination of Two Active Compounds That Bind to the Muscarinic M3 Receptor in Beer

Background: It is known that beer accelerates gastrointestinal motility in humans. Our previous studies showed that beer congener stimulates gastrointestinal motility by directly stimulating the muscarinic M₃ receptor. Further, we isolated 2 active compounds (compounds A and B) from beer by liquid chromatography. The objective of the present study was to identify the 2 active compounds that bind to the muscarinic M₃ receptor in beer.
Methods: Structural analyses of the active compounds were performed by fast atom bombardment mass spectra, ¹H-nuclear magnetic resonance (NMR), and ¹³C-NMR spectroscopy. Active compounds were chemically synthesized from p -coumaric acid and agmatine as starting materials. Binding activity to the muscarinic M₃ receptor was used to confirm the activity of the synthetic compounds.
Results: It was identified that 2 active compounds had the same structural characteristics: stereoisomers ( cis -isomer and trans -isomer), molecular weight=550 and molecular formula=C₂₈H₃₈N₈O₄. Trans -isomer (compound B) was identified as the known substance hordatine A, a kind of phytoalexin in barley, and cis -isomer (compound A) was found to be a novel compound (tentatively referred to as aperidine). Both naturally present and chemically synthesized aperidine (compound A) and hordatine A (compound B) were demonstrated to have potent binding activities to the muscarinic M₃ receptor.
Conclusions: The 2 active compounds isolated from beer, namely aperidine (compound A) and hordatine A (compound B), have structurally and functionally been identified as active entities of binding to the muscarinic M₃ receptor.     

Comparison of Haematological Features of the β0 and β+ Thalassaemia Traits in Jamaican Negroes

Haematological characteristics have been compared in 29 subjects with heterozygous β⁰ thalassaemia and in 33 subjects with heterozygous β⁺ thalassaemia, identified by the type of sickle cell-β thalassaemia among close relatives, in a Jamaican Negro population. Total haemoglobin, MCV and MCH were significantly lower in the β⁰ type but the level of Hb A₂ was not significantly different. Individual values for MCV, MCH and Hb A₂ in the β⁺ type occasionally overlapped those in the normal population casting doubt on the adequacy of these criteria in identifying all cases of heterozygous β⁺ thalassaemia. The haematological differences are those which would be expected on theoretical grounds. The inability to confidently differentiate the two types of heterozygous β thalassaemia has implications for genetic counselling. The inability to distinguish heterozygous β⁺ thalassaemia from normals on any single haematological index suggests that surveys depending on estimations of Hb A₂ or on MCV alone may have underestimated the prevalence of the β⁺ thalassaemia gene.