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At least 433 records · Page 24Linked to original sources
PubMed1990

Arrhythmias and alpha 1-adrenoceptor binding characteristics of the guinea-pig perfused heart during ischaemia and reperfusion.

Guinea-pig isolated hearts were perfused by the Langendorff method. Low flow (10%) global ischaemia for 30 min induced ventricular tachycardia (VT) and fibrillation (VF) in 87.5 and 37.5% respectively of the hearts. The onset times for VT and VF were 15.7 +/- 1.0 and 23.5 +/- 1.6 min respectively. On reperfusion the incidences of VT and VF were 81.3 and 75.0% and occurred after 16.0 +/- 1.5 and 35.0 +/- 4.9 s of reperfusion. In those hearts exhibiting arrhythmias, [3H]-prazosin binding to alpha 1-adrenoceptors of ventricular membrane fractions was measured and compared with normally perfused time-matched controls. There was no significant change in dissociation constant (KD) or density Bmax, of binding throughout the control perfusion period. Similarly, the KD (0.38 +/- 0.06 nM) and Bmax (15.5 +/- 1.4 fmol/mg protein) values obtained during ischaemia did not differ significantly from the corresponding control values (0.48 +/- 0.05 nM and 15.8 +/- 1.5 fmol/mg protein). Also, at 1 min of reperfusion the KD (0.42 +/- 0.04 nM) and Bmax (19.3 +/- 2.0 fmol/mg protein) values were not significantly different from the time-matched controls (0.38 +/- 0.09 nM and 20.1 +/- 2.6 fmol/mg protein). The same result was obtained if the crude membrane fraction pelleted by the initial slow spin was used. Thus, although cardiac arrhythmias are induced by ischaemia and reperfusion of the guinea-pig isolated perfused heart and previous studies have shown these to be susceptible to alpha-adrenoceptor blockade, they are not accompanied by an increase in alpha 1-adrenoceptor affinity or density.

Adrenergic Agonists↗
PubMed1984

A fundamental temperature-dependent difference between beta-adrenoceptor agonists and antagonists.

Positive inotropic and chronotropic responses of guinea-pig isolated left and right atria to sympathomimetic amines were examined at bath temperatures of 38, 30 or 25 degrees C. The concentration-response curves to isoproterenol and orciprenaline were displaced to the left by cooling, indicating hypothermia-induced supersensitivity. The affinities of isoproterenol and orciprenaline were determined as their dissociation constants (pKA) from antagonism of their responses by either the functional antagonist carbachol or Ro 03-7894 which is reported to be an irreversible beta-adrenoceptor antagonist. By both methods of calculation, the affinities of isoproterenol and orciprenaline for the beta-adrenoceptors mediating inotropic and chronotropic responses were increased by lowering the temperature. In contrast, the affinity of practolol, measured as the pA2 for competitive antagonism of the isoproterenol- and orciprenaline-induced inotropic and chronotropic responses, did not increase with cooling. Thus hypothermia-induced supersensitivity is associated with an increase in agonist affinity only, which indicates a fundamental temperature-dependent difference between agonist and antagonist interactions with the beta-adrenoceptor.

Animals↗
PubMed1983

The immunologic and ultrastructural characterization of the cellular infiltrate in acute cardiac allograft rejection: prevalence of cells with the natural killer (NK) phenotype.

The inflammatory cell infiltrates in 15 endomyocardial biopsies serially obtained from a human cardiac allograft during a 1 1/2-year period were characterized. An indirect immunofluorescent technique with hybridoma-derived monoclonal antibodies which preferentially react with B lymphocytes (anti-Ia), mature T cells (OKT3, Leu 1), and helper (OKT4b,d) and supressor/cytotoxic (OKT8) T-cell subsets and with natural killer cells, macrophages, and granulocytes (OKM1) was used. During each of seven rejection episodes the overwhelming majority of infiltrating cells in the endomyocardial biopsy were OKM1+Ia. These cells displayed short microvilli, a moderate amount of cytoplasm, numerous mitochondria, a large amount of rough endoplasmic reticulum, Golgi, and an indented nucleus, that is, the ultrastructural features of large, granular lymphocytes. Thus, they morphologically and phenotypically resemble those lymphoid cells which have been shown to possess natural killer (NK) functions in man. Occasional Leu 1+OKT3+ cells, some of which were OKT8+, were also seen during acute rejection. In each instance following therapy and resolution of the rejection episode only rare OKM1+Ia- cells were present. At this time the majority of the cells were Leu 1+OKT3+OKT8+. Routine biopsies, performed at times without evidence of rejection, showed only reactivity for Ia antigens by the capillary endothelium. These studies demonstrate the prevalence of cells with the natural killer phenotype in this human cardiac allograft during episodes of acute graft rejection.

Acute Disease↗
PubMed1985

The isolation and sequence of the gene encoding T8: a molecule defining functional classes of T lymphocytes.

The T cell surface glycoproteins T4 and T8 are thought to mediate efficient cell-cell interactions in the immune system and in this way may be responsible for the appropriate targeting of subpopulations of T cells. We have used gene transfer combined with subtractive hybridization to isolate both cDNA and functional genomic clones encoding the T8 protein. The sequence of the cDNA reveals that T8 is a transmembrane protein with an N-terminal domain which shares significant homology to immunoglobulin variable region light chains. This immunoglobulin-like structure is likely to be important in the function of T8 during differentiation and in the course of the immune response.

Amino Acid Sequence↗
PubMed1993

The family of genes encoding odorant receptors in the channel catfish.

The anatomical and numerical simplicity of the fish olfactory system has led us to examine the family of olfactory receptors expressed in the catfish. We have identified a family of genes encoding seven transmembrane domain receptors that share considerable homology with the odorant receptors of the rat. The size of the catfish receptor repertoire appears to be far smaller than in mammals. Analysis of the nucleotide sequences suggests that these receptor genes have undergone positive Darwinian selection to generate enhanced diversity within the putative odorant-binding domains. Individual receptor clones anneal with 0.5%-2% of the olfactory neurons, suggesting that a single cell expresses only a small subset of distinct odorant receptors. Each cell, therefore, possesses a unique identity defined by the receptors it expresses. These data suggest that the brain may discriminate among odors by determining which neurons have been activated.

Amino Acid Sequence↗
PubMed1993

Coding of olfactory information: topography of odorant receptor expression in the catfish olfactory epithelium.

Discrimination among the vast array of odors requires that the brain discern which of the numerous odorant receptors have been activated. If individual olfactory neurons express only a subset of the odorant receptor repertoire, then the nature of a given odorant can be discerned by identifying which cells have been activated. We performed in situ hybridization experiments demonstrating that individual olfactory neurons express different complements of odorant receptors and are therefore functionally distinct. Thus, a topographic map, defining either the positions of specific neurons in the epithelium or the positions of their projections, may be employed to determine the quality of an olfactory stimulus. Neurons expressing specific receptors appear to be randomly distributed within the olfactory epithelium. These data are consistent with a model in which randomly dispersed olfactory neurons with common receptor specificities project to common glomeruli in the olfactory bulb.

Animals↗
PubMed1987

Examination of cardiac alpha-adrenoceptors from pharmacological responses and radioligand binding. Comparison of rat and guinea pig tissues.

The object of this study was to determine suitable experimental conditions for the pharmacological evaluation of cardiac alpha-adrenoceptors. Atrial and ventricular preparations of the guinea pig and rat were employed, and the alpha-adrenoceptor responsiveness was compared with the binding of the alpha-adrenoceptor radioligand [3H]prazosin in membranes prepared from these cardiac regions. The experimental variables examined were the pacing frequency, bath temperature, choice of agonist, and cardiac region. In guinea pig atria the optimum alpha-adrenoceptor-mediated positive inotropic response to phenylephrine was at 32 degrees C and a pacing frequency of 1 Hz. A comparison of phenylephrine with methoxamine showed that the former yielded biphasic concentration-response curves in guinea pig left atria; the lower portion was alpha-adrenoceptor mediated and the upper, more substantial portion, was beta mediated. Methoxamine produced monophasic curves due entirely to alpha-adrenoceptor stimulation and was therefore used for comparisons between rat and guinea pig tissues. Of the guinea pig tissues, only the left atrium produced positive inotropic responses. Negative chronotropy was obtained with right atria and negative inotropy with ventricular strips and papillary muscles. The rat tissues all responded with positive responses, the largest maximum being in the left atrium. Binding data showed a larger number of alpha-adrenoceptors in the rat tissues, of which the ventricles had the greatest number. The lack of response of guinea pig ventricular tissues was therefore reflected in the low binding. From this study, the most appropriate model for characterizing cardiac alpha-adrenoceptors is therefore the rat left atria at 32 degrees C and paced at 1 Hz with methoxamine as the agonist.

Animals↗
PubMed1994

Isolation of cDNAs encoding T-BAM, a surface glycoprotein on CD4+ T cells mediating contact-dependent helper function for B cells: identity with the CD40-ligand.

"T-cell B-cell Activating Molecule" (T-BAM) is an activation-induced surface protein on CD4+ T cells that mediates a contact-dependent signal for B cell differentiation and immunoglobulin (Ig) secretion. The T-BAM protein on a helper clone of Jurkat (D1.1) was affinity purified using the anti-T-BAM mAb, 5c8. The NH2-terminal amino acid sequence of purified T-BAM was determined and found to be highly homologous to the predicted NH2-terminal sequence of a T cell ligand to the B cell CD40 molecule (CD40-L). From a D1.1 cDNA library, a clone was isolated that encodes CD40-L by sequence and drives expression of T-BAM protein on transfected cells, demonstrating that the T-BAM and CD40-L genes and proteins are identical. Moreover, transfection of T-BAM was shown to confer to non-lymphoid cells, the ability to induce B cells to upregulate the expression of surface CD23 molecules. In previous studies we showed that T-BAM was expressed predominantly on activated CD4+ and on few if any CD8+ cells. Although the current work confirms that T-BAM is largely restricted to activated CD4+ T cells, we now provide definitive evidence that T-BAM can be expressed by a small population of CD8+ T cells after activation. Importantly, a subset of CD8+ T cells do not express T-BAM after activation and this T-BAM- phenotype is maintained on certain CD8+ T cell clones. Taken together, these data unify the biology and structure of T-BAM and CD40-L and this synthesis has implications for understanding the T cell regulation of the humoral immune response.

Amino Acid Sequence↗
PubMed1983

A method for dissection of discrete regions of rat brain following microwave irradiation.

A simple microdissection technique for obtaining discrete areas from rat brains exposed to microwave irradiation is described and illustrated. Using the atlas of Pellegrino et al. [10] as a guide, stereotaxically defined areas were removed from coronal sections prepared with sectioning stages constructed from microscope slides. The dissection of sixteen discrete regions is shown in photographic and schematic form. This technique may prove useful for examining neurochemical processes in discrete areas of the rat central nervous system and may aid in establishing the distribution of pharmacological and toxicological agents at a neuroanatomical level.

Animals↗
PubMed1992

Molecular cloning and single-channel properties of the cyclic nucleotide-gated channel from catfish olfactory neurons.

We have cloned a functional cDNA encoding the cyclic nucleotide-gated channel selectively expressed in catfish olfactory sensory neurons. The cyclic nucleotide-gated channels share sequence and structural features with the family of voltage-gated ion channels. This homology is most evident in transmembrane region S4, the putative voltage sensor domain, and the H5 domain, thought to form the channel pore. We have characterized the single-channel properties of the cloned catfish channel and compared these properties with the channel in native catfish olfactory sensory neurons. The channel is activated equally well by cAMP and cGMP, shows only a slight voltage dependence of gating, and exhibits a pH- and voltage-dependent subconductance state similar to that observed for the voltage-gated L-type calcium channel.

Amino Acid Sequence↗
PubMed1993

Non-antigen signals for B-cell growth and differentiation to antibody secretion.

Recently, significant progress had been made in understanding the T-B lymphocyte interactions that control humoral immunity. This review highlights experiments that demonstrate a central role for interactions between T-cell-B-cell-activating molecule (CD40 ligand) expressed on T cells and CD40 on B cells in B-cell activation and immunoglobulin isotype switching, both in vitro and in vivo.

Animals↗
PubMed2006

Increased concentration of cerebral kynurenic acid alters stimulus processing and conditioned responding.

Kynurenic acid (KYNA) is a tryptophan metabolite synthesized and released by glia and recently shown to be a non-competitive antagonist of alpha7 nicotinic acetylcholine receptors at physiologically relevant concentrations, and NMDA receptors at higher concentrations. KYNA concentration is elevated in individuals with schizophrenia and those with Alzheimer's disease, two populations exhibiting cholinergic-related cognitive impairments. The present study investigated the effects of elevated KYNA concentration on conditioned stimulus processing in rats. For the first 2 days of the experiment, a subset of rats received intracerebroventricular infusions of either KYNA (0.1 microM) or vehicle and were either returned to the home cage or received non-reinforced presentations of a visual stimulus. All rats subsequently received presentations of the same visual stimulus followed by food reward during a 6-day training phase. In vehicle-treated rats, pre-exposure to the visual stimulus reduced orienting behaviour to the light (standing on the hind legs and orienting towards the visual stimulus) when it was later reinforced (i.e., conditioned orienting). In contrast, pre-exposure to the visual cue or 2 days of KYNA pretreatment reduced conditioned orienting behaviour. Finally, the reduction of orienting in KYNA-treated rats following pre-exposure was not as robust as in vehicle-treated rats. These results suggest that elevated KYNA levels can alter specific aspects of attentional processing of environmental stimuli and are discussed in terms of the potential contribution of KYNA to cognitive function and dysfunction.

Analysis of Variance↗
PubMed2006

Potential impact of carbohydrate and fat intake on pathological left ventricular hypertrophy.

Currently, a high carbohydrate/low fat diet is recommended for patients with hypertension; however, the potentially important role that the composition of dietary fat and carbohydrate plays in hypertension and the development of pathological left ventricular hypertrophy (LVH) has not been well characterized. Recent studies demonstrate that LVH can also be triggered by activation of insulin signaling pathways, altered adipokine levels, or the activity of peroxisome proliferator-activated receptors (PPARs), suggesting that metabolic alterations play a role in the pathophysiology of LVH. Hypertensive patients with high plasma insulin or metabolic syndrome have a greater occurrence of LVH, which could be due to insulin activation of the serine-threonine kinase Akt and its downstream targets in the heart, resulting in cellular hypertrophy. PPARs also activate cardiac gene expression and growth and are stimulated by fatty acids and consumption of a high fat diet. Dietary intake of fats and carbohydrate and the resultant effects of plasma insulin, adipokine, and lipid concentrations may affect cardiomyocyte size and function, particularly in the setting of chronic hypertension. This review discusses potential mechanisms by which dietary carbohydrates and fats ca affect cardiac growth, metabolism, and function, mainly in the context of pressure overload-induced LVH.

Adiponectin↗
PubMed2006

Depressed contractile responses to neurokinin A in idiopathic but not neurogenic overactive human detrusor muscle.

OBJECTIVE: The role of tachykinins such as neurokinin A in regulating bladder function is unclear, but NK2 receptors seem to mediate contraction in the human bladder and it has been suggested that these peptides may have a role in the pathophysiology of bladder dysfunction. The present study investigates neurokinin receptor-mediated contractility of detrusor muscle in the idiopathic overactive and neurogenic overactive bladder and investigates the neurokinin receptor subtypes involved. METHODS: Human bladder was obtained from patients undergoing cystectomy (normal) or clam cystoplasty (idiopathic overactive) and from patients with spinal injuries (neurogenic overactive). Strips of isolated detrusor muscle were mounted in physiological Krebs-bicarbonate solution and cumulative concentration-response curves to 1 nM to 300 microM neurokinin A (NKA) were obtained in the absence and presence of neurokinin receptor antagonists, either the NK2 receptor-selective antagonist SR 48968 or the NK3 receptor-selective antagonist SB 223412. RESULTS: NKA evoked concentration-dependent contraction of normal, idiopathic, and neurogenic overactive detrusor strips. In idiopathic overactive detrusor muscle, NKA-induced contraction was significantly reduced relative to normal detrusor (0.031 +/- 0.005 mg/g, n = 11 versus 0.193 +/- 0.039 mg/g, n = 7). Sensitivity to the peptide was also significantly (p < 0.01) reduced in idiopathic overactive detrusor, with mean pEC50 values (concentration producing 50% maximal response) of 6.62+/-0.16 (n = 11) compared to 7.47+/-0.19 (n = 7) in normal detrusor. In contrast, NKA-induced responses of neurogenic overactive detrusor were similar to those in normal detrusor, with a mean maximum contraction of 0.199 +/- 0.036 mg/g (n = 10) and mean pEC50 value of 7.85+/-0.16 (n = 10). NKA curves in all groups were shifted to the right by the NK2 receptor-selective antagonist SR 48968 with high affinity, pK(B) values being similar in normal, idiopathic, and neurogenic overactive detrusor (8.85 + 0.08, n = 14; 8.97 +/- 0.13, n = 12; 8.73 +/- 0.12, n = 8, respectively). In contrast the NK3 receptor-selective antagonist SB 223412 had a minimal effect on NKA responses and affinity values were low (pK(B) 5.81 +/- 0.11, n = 12 in normal; 5.75 +/- 0.08, n = 12 in idiopathic overactive, and 5.77 +/- 0.13, n = 11 in neurogenic overactive). CONCLUSION: These data indicate that NKA-induced responses are impaired in detrusor muscle from idiopathic overactive human bladder, but not in detrusor muscle from neurogenic overactive bladder. The NK2 receptor subtype appears to mediate NKA responses in the normal, idiopathic overactive, and neurogenic overactive detrusor. This is important evidence suggesting a difference between the bladder pathophysiology observed in idiopathic versus neurogenic overactive detrusor.

Benzamides↗
PubMed2006

Human idiopathic and neurogenic overactive bladders and the role of M2 muscarinic receptors in contraction.

OBJECTIVES: This study examines whether M(2) receptors contribute to direct contraction of the detrusor in human neurogenic and idiopathic overactive bladders. METHODS: Control detrusor muscle was obtained from patients undergoing cystectomy for bladder cancer, whilst overactive detrusor muscle was obtained from patients undergoing clam cystoplasty for idiopathic or neurogenic detrusor overactivity. The affinities of a range of subtype selective antagonists (DAMP, darifenacin, methoctramine R0-320-6206, and pirenzepine) were obtained in tissue bath experiments by using carbachol as the agonist. These affinity values were then compared with the known affinities for these antagonists at the muscarinic receptor subtypes. RESULTS: An increased sensitivity to carbachol was observed in both the neurogenic and idiopathic overactive detrusors compared with the control human detrusor. The M(2)-selective antagonists (methoctramine, R0-320-6206) and M(1)-selective antagonist (pirenzepine) had low affinities, whilst the M(3)-selective antagonists (4-DAMP and darifenacin) had high affinities for the human detrusor muscarinic receptor in all three groups of tissues. The affinities (pK(B) values) for the five antagonists were consistent with antagonisms at the M(3) receptor in all three groups; Schild plot analysis indicated an action at this single receptor subtype. CONCLUSIONS: Contraction mediated by muscarinic receptors is enhanced in idiopathic and neurogenic overactive detrusors compared with control detrusor. The direct contractile response to carbachol is mediated by the M(3) receptor in both human normal and overactive bladders, indicating no change in receptor subtype contribution to contraction in the disease state.

Adult↗