InGaN µLEDs integrated onto colloidal quantum dot functionalized ultra-thin glass.

Red-, orange-, and green-emitting integrated optoelectronic sources are demonstrated by transfer printing blue InGaN µLEDs onto ultra-thin glass platforms functionally enhanced with II-VI colloidal quantum dots (CQDs). The forward optical power conversion efficiency of these heterogeneously integrated devices is, respectively, 9%, 15%, and 14% for a blue light absorption over 95%. The sources are demonstrated in an orthogonal frequency division multiplexed (OFDM) visible light communication link reaching respective data transmission rates of 46 Mbps, 44 Mbps and 61 Mbps.

Heterogeneous integration of gallium nitride light-emitting diodes on diamond and silica by transfer printing.

We report the transfer printing of blue-emitting micron-scale light-emitting diodes (micro-LEDs) onto fused silica and diamond substrates without the use of intermediary adhesion layers. A consistent Van der Waals bond was achieved via liquid capillary action, despite curvature of the LED membranes following release from their native silicon growth substrates. The excellence of diamond as a heat-spreader allowed the printed membrane LEDs to achieve optical power output density of 10 W/cm(2) when operated at a current density of 254 A/cm(2). This high-current-density operation enabled optical data transmission from the LEDs at 400 Mbit/s.

Efficiency droop in zincblende InGaN/GaN quantum wells.

The decrease in emission efficiency with increasing drive current density, known as 'droop', of c-plane wurtzite InGaN/GaN quantum wells presently limits the use of light-emitting diodes based on them for high brightness lighting applications. InGaN/GaN quantum wells grown in the alternative zincblende phase are free of the strong polarisation fields that exacerbate droop and so were investigated by excitation-dependent photoluminescence and photoreflectance studies. Polarisation-resolved measurements revealed that for all excitation densities studied the emission from such samples largely originates from similar microstructures or combinations of microstructures that form within the quantum well layers. Emission efficiency varies significantly with excitation at 10 K showing that non-radiative recombination processes are important even at low temperature. The onset of efficiency droop, as determined by photomodulated reflection measurements, occurred at a carrier density of around 1.2 × 1020 cm-3 - an order of magnitude greater than the value reported for a reference wurtzite quantum well sample using the same method. The high carrier density droop onset combined with the much shorter carrier lifetime within zincblende InGaN/GaN quantum wells indicate they have the potential to effectively delay efficiency droop when used in GaN based light-emitting diodes. However, the material quality of the quantum well layers need to be improved by preventing the formation of microstructures within these layers, and the importance of the role played by non-radiative centres in the QW layer needs to be elucidated, to fully realise the material's potential.

Prospects of III-nitride optoelectronics grown on Si.

The use of III-nitride-based light-emitting diodes (LEDs) is now widespread in applications such as indicator lamps, display panels, backlighting for liquid-crystal display TVs and computer screens, traffic lights, etc. To meet the huge market demand and lower the manufacturing cost, the LED industry is moving fast from 2 inch to 4 inch and recently to 6 inch wafer sizes. Although Al2O3 (sapphire) and SiC remain the dominant substrate materials for the epitaxy of nitride LEDs, the use of large Si substrates attracts great interest because Si wafers are readily available in large diameters at low cost. In addition, such wafers are compatible with existing processing lines for 6 inch and larger wafers commonly used in the electronics industry. During the last decade, much exciting progress has been achieved in improving the performance of GaN-on-Si devices. In this contribution, the status and prospects of III-nitride optoelectronics grown on Si substrates are reviewed. The issues involved in the growth of GaN-based LED structures on Si and possible solutions are outlined, together with a brief introduction to some novel in situ and ex situ monitoring/characterization tools, which are especially useful for the growth of GaN-on-Si structures.

Mutations in the homeodomain of the human SIX3 gene cause holoprosencephaly.

Holoprosencephaly (HPE) is a common, severe malformation of the brain that involves separation of the central nervous system into left and right halves. Mild HPE can consist of signs such as a single central incisor, hypotelorism, microcephaly, or other craniofacial findings that can be present with or without associated brain malformations. The aetiology of HPE is extremely heterogeneous, with the proposed participation of a minimum of 12 HPE-associated genetic loci as well as the causal involvement of specific teratogens acting at the earliest stages of neurulation. The HPE2 locus was recently characterized as a 1-Mb interval on human chromosome 2p21 that contained a gene associated with HPE. A minimal critical region was defined by a set of six overlapping deletions and three clustered translocations in HPE patients. We describe here the isolation and characterization of the human homeobox-containing SIX3 gene from the HPE2 minimal critical region (MCR). We show that at least 2 of the HPE-associated translocation breakpoints in 2p21 are less than 200 kb from the 5' end of SIX3. Mutational analysis has identified four different mutations in the homeodomain of SIX3 that are predicted to interfere with transcriptional activation and are associated with HPE. We propose that SIX3 is the HPE2 gene, essential for the development of the anterior neural plate and eye in humans.

'Sink or swim': an evaluation of the clinical characteristics of individuals with high bone mass.

SUMMARY: High bone mineral density on routine dual energy X-ray absorptiometry (DXA) may indicate an underlying skeletal dysplasia. Two hundred fifty-eight individuals with unexplained high bone mass (HBM), 236 relatives (41% with HBM) and 58 spouses were studied. Cases could not float, had mandible enlargement, extra bone, broad frames, larger shoe sizes and increased body mass index (BMI). HBM cases may harbour an underlying genetic disorder. INTRODUCTION: High bone mineral density is a sporadic incidental finding on routine DXA scanning of apparently asymptomatic individuals. Such individuals may have an underlying skeletal dysplasia, as seen in LRP5 mutations. We aimed to characterize unexplained HBM and determine the potential for an underlying skeletal dysplasia. METHODS: Two hundred fifty-eight individuals with unexplained HBM (defined as L1 Z-score ≥ +3.2 plus total hip Z-score ≥ +1.2, or total hip Z-score ≥ +3.2) were recruited from 15 UK centres, by screening 335,115 DXA scans. Unexplained HBM affected 0.181% of DXA scans. Next 236 relatives were recruited of whom 94 (41%) had HBM (defined as L1 Z-score + total hip Z-score ≥ +3.2). Fifty-eight spouses were also recruited together with the unaffected relatives as controls. Phenotypes of cases and controls, obtained from clinical assessment, were compared using random-effects linear and logistic regression models, clustered by family, adjusted for confounders, including age and sex. RESULTS: Individuals with unexplained HBM had an excess of sinking when swimming (7.11 [3.65, 13.84], p < 0.001; adjusted odds ratio with 95% confidence interval shown), mandible enlargement (4.16 [2.34, 7.39], p < 0.001), extra bone at tendon/ligament insertions (2.07 [1.13, 3.78], p = 0.018) and broad frame (3.55 [2.12, 5.95], p < 0.001). HBM cases also had a larger shoe size (mean difference 0.4 [0.1, 0.7] UK sizes, p = 0.009) and increased BMI (mean difference 2.2 [1.3, 3.1] kg/m(2), p < 0.001). CONCLUSION: Individuals with unexplained HBM have an excess of clinical characteristics associated with skeletal dysplasia and their relatives are commonly affected, suggesting many may harbour an underlying genetic disorder affecting bone mass.

A common variant of the latrophilin 3 gene, LPHN3, confers susceptibility to ADHD and predicts effectiveness of stimulant medication.

Attention-Deficit/Hyperactivity Disorder (ADHD) has a very high heritability (0.8), suggesting that about 80% of phenotypic variance is due to genetic factors. We used the integration of statistical and functional approaches to discover a novel gene that contributes to ADHD. For our statistical approach, we started with a linkage study based on large multigenerational families in a population isolate, followed by fine mapping of targeted regions using a family-based design. Family- and population-based association studies in five samples from disparate regions of the world were used for replication. Brain imaging studies were performed to evaluate gene function. The linkage study discovered a genome region harbored in the Latrophilin 3 gene (LPHN3). In the world-wide samples (total n=6360, with 2627 ADHD cases and 2531 controls) statistical association of LPHN3 and ADHD was confirmed. Functional studies revealed that LPHN3 variants are expressed in key brain regions related to attention and activity, affect metabolism in neural circuits implicated in ADHD, and are associated with response to stimulant medication. Linkage and replicated association of ADHD with a novel non-candidate gene (LPHN3) provide new insights into the genetics, neurobiology, and treatment of ADHD.

Detection of Bartonella infection in pet dogs from Manila, the Philippines.

Dogs can be infected by a wide range of Bartonella spp., but studies regarding the prevalence of Bartonella infection in dogs in the Philippines have not been conducted. This study aimed at determining the prevalence of Bartonella infection in pets dogs from two veterinary clinics in Metro Manila, The Philippines, using both serology and polymerase chain reaction (PCR). Blood samples from 116 dogs from two different groups, one of 60 mainly "healthy dogs" and the other one of 56 dogs enrolled in a tick-borne disease suspect group, were tested for presence of B. henselae antibodies and to detect Bartonella DNA using primers specific for the citrate synthase gene. Seroprevalence for B. henselae was very low (2.6%), as the only three (5%) seropositive dogs (titer 1:64) where among the healthy pet dog group. Following subsequent sequencing, 13 samples, all from the tick-borne disease group, were determined positive for B. henselae (11.2%). This is the first study to report dog infection with B. henselae in the Philippines.

Emotions and eating. Self-reported and experimentally induced changes in food intake under stress.

Two studies investigated the stress-eating relationship. The first examined self-reported changes in intake of snack foods, whilst the second investigated stress-induced overconsumption in a laboratory setting comparing high (HF) and low-fat (LF) snacks. Eighty-nine females completed the Dutch Eating Behaviour Questionnaire (DEBQ) [Van Strien, T., Fritjers, J. E. R., Bergers, G. P. A., & Defares, P. B. (1986). Dutch Eating Behaviour Questionnaire for assessment of restrained, emotional and external eating behaviour. International Journal of Eating Disorders, 5, 295-315] and a self-report measure designed to evaluate changes in eating in response to stress. Increased intake of HF snacks was associated with high emotional eating but not with restraint. A laboratory-based experiment compared intake of HF and LF snacks after ego-threatening and neutral Stroop colour-naming tasks. Intake was suppressed by 31.8% in restrained compared to unrestrained eaters across tasks. Restrained eaters consumed significantly less after ego-threat than after the neutral manipulation, but this was associated only with intake of the LF snack. Restrained eaters' intake of dried fruit was suppressed by 33.2% after ego-threat relative to the neutral task, despite a significant increase in hunger for this group following ego-threat. These results suggest that the type and variety of foods offered influences the link between stress and eating in laboratory settings. Further research should aim to replicate and extend these findings, with a view to informing potential interventions for stress-related eating.

High Prevalence of Bartonella sp. in Dogs from Hamadan, Iran.

Bartonellae are emerging vector-borne pathogens infecting various domestic and wild mammals. Blood samples were collected from 66 dogs at two locations near Hamedan, Iran. Twenty dogs were rescued stray dogs and 46 dogs were from a breeding colony, with many of them infested with fleas, ticks, or lice. Serology was performed using an indirect immunofluorescent antibody test for Bartonella henselae, Bartonella clarridgeiae, and Bartonella vinsonii subsp. berkhoffii. Seroprevalence was 74.2% (range: 65.2-95%). Bartonella DNA amplification and sequencing identified B. vinsonii subsp. berkhoffii type III in seven dogs, including five rescued dogs. Two dogs were infected with Bartonella rochalimae and three dogs with Candidatus B. merieuxii, including two of the stray dogs coinfected with Bartonella vinsonii subsp. berkhoffii. Rescued stray dogs were 10 times (odds ratio (OR) = 10.13, 95% CI: 1.24-82.7; P = 0.03) more likely to be seropositive and eight times (OR = 8.82, 95% CI: 2.68-29.11; P = 0.0004) more likely to be flea-infested than breeding dogs, confirming that arthropod infestation is a major risk factor for these infections.

Progressive multifocal leukoencephalopathy associated with infliximab.

A 69-year-old female with seropositive rheumatoid arthritis presented with progressive cognitive decline following treatment with infliximab and methotrexate. Cranial MRI showed non-enhancing white matter signal abnormality consistent with demyelination was seen in the antero-inferior left frontal lobe extending into the frontal opercular white matter and into the left temporal lobe white matter. Similar appearances were seen in the inferomedial right frontal lobe. Brain biopsy showed histological changes consistent with progressive multifocal leukoencephalopathy. The cerebrospinal fluid polymerase chain reaction was negative but brain tissue polymerase chain reaction was positive for JC virus. This case highlights the association of infliximab with progressive multifocal leukoencephalopathy in a patient with known seropositive rheumatoid arthritis.

Argatroban anticoagulant therapy in patients with heparin-induced thrombocytopenia.

BACKGROUND: Heparin-induced thrombocytopenia (HIT) is an immune-mediated syndrome caused by heparin. Complications range from thrombocytopenia to thrombocytopenia with thrombosis. We report a prospective, historical- controlled study evaluating the efficacy and safety of argatroban, a direct thrombin inhibitor, as anticoagulant therapy in patients with HIT or HIT with thrombosis syndrome (HITTS). METHODS AND RESULTS: Patients with HIT (isolated thrombocytopenia, n=160) or HITTS (n=144) received 2 microgram. kg(-1). min(-1) IV argatroban, adjusted to maintain the activated partial thromboplastin time 1.5 to 3.0 times baseline value. Treatment was maintained for 6 days, on average. Clinical outcomes over 37 days were compared with those of 193 historical control subjects with HIT (n=147) or HITTS (n=46). The incidence of the primary efficacy end point, a composite of all-cause death, all-cause amputation, or new thrombosis, was reduced significantly in argatroban-treated patients versus control subjects with HIT (25.6% versus 38.8%, P=0.014). In HITTS, the composite incidence in argatroban-treated patients was 43.8% versus 56.5% in control subjects (P=0.13). Significant between-group differences by time-to-event analysis of the composite end point favored argatroban treatment in HIT (P=0.010) and HITTS (P=0.014). Argatroban therapy, relative to control subjects, also significantly reduced new thrombosis and death caused by thrombosis (P<0.05). Argatroban-treated patients achieved therapeutic activated partial thromboplastin times generally within 4 to 5 hours of starting therapy and, compared with control subjects, had a significantly more rapid rise in platelet counts (P=0.0001). Bleeding events were similar between groups. CONCLUSIONS: Argatroban anticoagulation, compared with historical control subjects, improves clinical outcomes in patients who have heparin-induced thrombocytopenia, without increasing bleeding risk.

5-HT receptors involved in initiation or modulation of motor patterns: opportunities for drug development.

A clearer understanding of the role of descending systems in motor control can be achieved by using in vitro preparations of mammalian spinal cord that display patterned motor output, together with the use of selective pharmacological agents. It has been suggested that 5-HT is involved in either the initiation or the modulation of certain motor behaviours, and that it acts to enhance or regulate the motor pattern. Most attention has been paid to the locomotor rhythms underlying walking or swimming, and in respiratory pattern generation. In this article, David Wallis discusses the involvement of 5-HT1 and 5-HT2 receptors in these processes and the possible therapeutic relevance.

Segmental wall motion abnormalities in dilated cardiomyopathy: a common finding and good prognostic sign.

Fifty patients with idiopathic dilated cardiomyopathy were separated into two groups based on the presence of segmental or diffuse left ventricular wall motion abnormalities by radionuclide ventriculography. Investigation included a history and physical examination, electrocardiogram, chest X-ray film, M-mode echocardiogram, coronary angiogram and right ventricular endomyocardial biopsy. Patients with histologic evidence of myocarditis were excluded. Sixty-four percent of the patients had segmental and 36% had diffuse wall motion abnormalities. The group with segmental abnormalities showed significant differences in age (52.5 +/- 10.7 versus 37.8 +/- 14.6 years, p less than 0.001), New York Heart Association functional class III to IV (56 versus 89%, p less than 0.01), pulmonary capillary wedge pressure (14 +/- 9 versus 26 +/- 9 mm Hg, p less than 0.001), left ventricular end-diastolic dimension measured on echocardiogram (67 +/- 8 versus 77 +/- 11 mm, p less than 0.001), cardiac index (2.6 +/- 0.6 versus 2.0 +/- 0.5 liters/min per m2, p less than 0.01) and ejection fraction by radionuclide ventriculography (20 +/- 7 versus 13 +/- 5%, p less than 0.001). Patients with diffuse wall motion abnormalities had poorer histologic findings based on myocardial cell hypertrophy and nuclear changes (p less than 0.01) and a higher short-term mortality with a 1 year survival rate of 50% compared with 90% in patients with segmental wall motion abnormalities by life-table analysis (p less than 0.05). When data were reanalyzed excluding those patients with complete left bundle branch block, no significant change in any variable was detected. Segmental wall motion abnormalities, even when left bundle branch block is excluded, are common in dilated cardiomyopathy in the absence of coronary artery disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Transesophageal echocardiographic assessment of the contribution of intrinsic tissue thickness to the appearance of a thick mitral valve in patients with mitral valve prolapse.

OBJECTIVES: This prospective, blinded transesophageal echocardiographic study was performed to determine the relative contributions of leaflet redundancy and overlap versus intrinsic tissue thickening as mechanisms for the apparent increase in diastolic thickness of the mitral valve. BACKGROUND: Increased diastolic thickness of the mitral valve has been identified as an echocardiographic feature that predicts subsequent adverse sequelae in patients with mitral valve prolapse (MVP). METHODS: Eleven patients with clinical and transthoracic echocardiographic evidence of MVP and 11 age-matched control subjects underwent protocol transesophageal echocardiography to image the mitral valve in two orthogonal planes and to measure its thickness in systole and diastole. RESULTS: Maximal diastolic width of the slack, unloaded anterior leaflet was significantly greater in patients with MVP than in control subjects (mean +/- SD: 0.64 +/- 0.20 cm vs. 0.30 +/- 0.04 cm, p < 0.001). Similarly, diastolic posterior leaflet width was greater in patients with MVP (0.67 +/- 0.39 cm vs. 0.31 +/- 0.06 cm, p < 0.01). In contrast, minimal systolic width of the distended pressure-loaded mitral valve was not significantly different between patients with MVP and control subjects for either the anterior (0.22 +/- 0.05 cm vs. 0.20 +/- 0.04 cm, p = NS) or the posterior (0.25 +/- 0.07 cm vs. 0.24 +/- 0.05 cm, p = NS) leaflets. The percent change in leaflet width from diastole to systole (% delta W), an index of the contribution of dynamic factors (e.g., leaflet redundancy and overlap) to the apparent increase in diastolic leaflet thickness, was significantly greater in patients with MVP than in control subjects for both the anterior (% delta W 62 +/- 13% vs. 34 +/- 16%, p < 0.001) and the posterior (% delta W 54 +/- 19% vs. 22 +/- 21%, p < 0.005) leaflets. CONCLUSIONS: The apparent increase in diastolic mitral leaflet thickness in patients with MVP versus control subjects is largely attributable to dynamic factors such as leaflet redundancy, overlap and deformation. During diastole, when the mitral leaflets are slack and unstressed, the leaflets appear markedly thickened in patients with MVP. In contrast, during systole, when developed intraventricular pressure distends the leaflets, causing them to stretch and balloon into the left atrium, the intrinsic tissue thickness is much less than that measured in diastole. These findings have important implications for the morphologic criteria used to diagnose MVP and the potential pathophysiologic mechanisms for adverse sequelae in this syndrome.

Peripartum cardiomyopathy: clinical, hemodynamic, histologic and prognostic characteristics.

Peripartum cardiomyopathy is defined as left ventricular dilation and failure, first developing during the third trimester of pregnancy or in the first 6 months postpartum. In an effort to characterize this syndrome in a middle class population, 14 consecutive patients with peripartum cardiomyopathy underwent a detailed history and physical examination, right heart catheterization, M-mode and two-dimensional echocardiography, radionuclide ventriculography and right ventricular endomyocardial biopsy. These patients were then observed with sequential noninvasive studies to determine prognostic indicators. Eight (57%) of these 14 patients were primiparous and an equal number first presented with heart failure concomitant with or immediately before the onset of labor. When these women were compared with 55 patients with idiopathic dilated cardiomyopathy, only mean age at onset of symptoms (28.7 +/- 5.7 versus 48.2 +/- 13.6 years, p less than 0.001) and symptom duration (4.1 +/- 7.7 versus 19.0 +/- 18.4 months, p less than 0.001) differed between the groups. There was no difference in ventricular arrhythmia, left ventricular chamber size, ejection fraction or hemodynamics. Myocyte histologic findings were similar; however, myocarditis was identified in 29% of patients with peripartum cardiomyopathy and in only 9% of those with idiopathic dilated cardiomyopathy. In all patients with peripartum cardiomyopathy and myocarditis, the myocardial biopsy was performed within 1 week of onset of symptoms. Seven (50%) of the patients with peripartum cardiomyopathy had dramatic improvement within 6 weeks of follow-up, and 6 (43%) died.(ABSTRACT TRUNCATED AT 250 WORDS)

Failure of early heparin cessation as treatment for heparin-induced thrombocytopenia.

PURPOSE: The complications of heparin-induced thrombocytopenia include thrombosis and death. The purpose of the study was to determine whether early heparin cessation can prevent these outcomes. SUBJECTS AND METHODS: We performed a retrospective analysis of consecutive patients with heparin-induced thrombocytopenia diagnosed by platelet aggregometry. Demographic, clinical, and laboratory findings were compared in patients by whether heparin treatment was stopped early (< or = 48 hours) or late (>48 hours) after the onset of thrombocytopenia, as well as between patients with and without thrombosis. Thrombocytopenia was defined as a 50% decline in baseline platelet counts or an absolute platelet count < 100,000/mm3. RESULTS: Of the 113 patients, 38% developed thrombosis and 27% died. One-half of patients had thrombosis diagnosed >24 hours after heparin cessation. No difference in thrombosis or mortality was found in the 40 patients with early heparin cessation [mean (+/-SD) time of cessation 0.7 +/- 0.6 days] compared with the 73 patients with late heparin cessation (5 +/- 3 days). Thrombosis >24 hours after heparin cessation occurred in 61% of the patients in the early group and in 40% of the late group (P = 0.17). In a multivariate analysis, only a lower nadir of the platelet count (percent of baseline) was associated with thrombosis. Neither thrombosis nor the time to heparin cessation were associated with mortality. CONCLUSIONS: Early heparin cessation was not effective in reducing morbid events in patients with heparin-induced thrombocytopenia. Treatment strategies other than heparin cessation alone should be considered in patients with this condition.

Further studies on the blockade of 5-HT depolarizations of rabbit vagal afferent and sympathetic ganglion cells by MDL 72222 and other antagonists.

The blocking action of MDL 72222 (1 alpha H, 3 alpha, 5 alpha H-tropan-3-yl-3, 5-dichlorobenzoate at 5-hydroxytryptamine (5-HT) receptors on nodose (NG) and superior cervical ganglia (SCG) has been investigated further. The sucrose-gap technique was used to record potential changes from populations of neurones. The surmountable blockade induced by small concentrations of the antagonist was quantified and the blocking potency compared with that of a number of other compounds. In nodose ganglia three 4-5 point dose-response (DR) curves were established, using bolus injections of 5-HT (5-80 nmol). The mean amplitude of the response to 80 nmol was 4.18 +/- 0.53 mV and the ED50 was 18.2 nmol. Second and 3rd dose-response curves showed small displacements to the right, indicating a slight reduction in sensitivity. In superior cervical ganglia responsiveness was less. Amounts of 5-HT ranging from 20 to 320 nmol evoked dose-related depolarizations. The mean amplitude of the response evoked by 320 nmol 5-HT was 1.7 +/- 0.14 mV. Three 4-5 point dose-response curves could be elicited from a single ganglion. The ED50 was 55.8 nmol. Initial, 2nd and 3rd dose-response curves could be superimposed, there being no significant rightward shift. The results confirm that MDL 72222 is a potent, selective antagonist at 5-HT receptors in nodose and superior cervical ganglia. In the nodose ganglion, after equilibration for 1 hr with 10(-8) or 10(-7) M MDL 72222, dose-response curves for 5-HT showed rightward, parallel shifts. In contrast, 10(-6) M MDL 72222 or prolonged exposure (3-4 hr) to 10(-8), 10(-7) or 10(-6) M caused larger rightward shifts of the dose-response curves and depressed the maximum responses. In the superior cervical ganglion, equilibration for 1 hr with concentrations of 10(-8) or 10(-7) M produced effects on the dose-response curves similar to those seen in the nodose ganglion, but longer exposures (3-4 hr) did not depress the maximum. Apparent pA2 values were determined from individual experiments on both the nodose and superior cervical ganglia, where MDL 72222 (10(-7) M or less, for 1 hr) caused parallel or near parallel shifts of dose-response curves. In the nodose ganglion the apparent pA2 was 7.7 +/- 0.1, while in the superior cervical ganglion it was 7.8 +/- 0.1 (mean +/- SEM). The nature of the blockade induced by prolonged exposures or by concentrations greater than 10(-7) M is discussed.(ABSTRACT TRUNCATED AT 400 WORDS)

5-Hydroxytryptamine depolarizes neonatal rat motorneurones through a receptor unrelated to an identified binding site.

Superfusion of hemisected lumbar spinal cord of the neonatal rat with solutions containing 10(-6) to 10(-3) M 5-hydroxytryptamine (5-HT) elicited depolarizations of graded amplitude which were recorded from motorneurons through a ventral root. Maximum responses (amplitude 1.0 +/- 0.1 mV, mean +/- SEM, n = 30) were evoked by 10(-4) M 5-HT. Repeated concentration-response curves could be determined from the same preparation. There was no involvement of 5-HT2 receptors in the depolarizing response to 5-HT, since neither ritanserin nor ICI 169, 369 showed any antagonist action. Amongst agents with activity at 5-HT1A sites, the selective 5-HT1A receptor agonist, 8-hydyroxy-2-(di-N-propylamino) tetralin (8-OH-DPAT), neither mimicked the action of 5-HT nor antagonised it, while spiperone (10(-8)-10(-7 M) antagonised responses to 5-HT in a concentration-related manner. Responses to 10(-4) M noradrenaline, used as a control depolarizing agent, were unaffected by spiperone. The onset of blockade by spiperone was slow, 1 hr being required for equilibration of the tissue with antagonist. The blockade was surmountable by larger concentrations of 5-HT. Concentration-response curves to 5-HT were shifted to the right in an approximately parallel manner by spiperone. The dose ratios measured from these curves at the EC50 level, yielded an apparent pA2 of 8.24 +/- 0.14 (mean +/- SEM, n = 15), although the Schild plot of the data had a slope less than unity. The lack of activity of the selective 5-HT1B receptor agonist, RU 24969, and the 5-HT1B receptor antagonists, (+/-) cyanopindolol and quipazine, indicated that 5-HT1B receptors were not involved in the 5-HT response of motorneurones to 5-HT. Mesulergine, metergoline and cyproheptadine also antagonised responses of motorneurones to 5-HT, producing a surmountable blockade. Mesulergine (10(-8), 3 x 10(-8) and 10(-7) M caused a progressive rightward shift of the concentration-response curves, but 10(-7) M depressed the maximum response to 5-HT. Responses to noradrenaline were not affected by these concentrations of mesulergine. The apparent pA2 for blockade of 5-HT responses by mesulergine, calculated from experiments in which there was a parallel displacement of the concentration-response curves, was 8.75 +/- 0.11 (mean +/- SEM, n = 10).(ABSTRACT TRUNCATED AT 400 WORDS)