Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. Achatin-I (Gly-D-Phe-L-Ala-L-Asp), a neuroactive tetrapeptide having a D-phenylalanine residue, has been proposed to be an excitatory neurotransmitter of Achatina giant neurons. It was revealed that the D-Phe2 residue is essential for bioactivity of achatin-I, which seems to adopt beta-turn conformation. In the present study, in order to investigate the structure-activity relationships of achatin-I and its derivatives, the two highly constrained analogs of achatin-I, [delta ZPhe2]achatin-I (Gly-delta ZPhe-L-Ala-L-Asp) (delta ZPhe: (Z)-alpha,beta-dehydrophenylalanine) and [Aib2]achatin-I (Gly-Aib-L-Ala-L-Asp) (Aib: alpha-aminoisobutyric acid), were synthesized, and their effects on the two identifiable Achatina giant neuron types, PON (periodically oscillating neuron) and v-RCDN (ventral-right cerebral distinct neuron), were examined in comparison with those of achatin-I under voltage clamp. 2. Achatin-I (n = 6), ejected onto the neurone by brief pneumatic pressure (2 kg/cm2, 400 ms, 10(-3) M, at 10-min intervals), produced an inward current (Im) on PON. The Iin value (mean +/- SEM) was 0.44 +/- 0.03 nA. The interval between the achatin-I ejection and the Iin peak was 14.74 +/- 3.15 s (n = 6). [delta ZPhe2]achatin-I (n = 6) and [Aib2]achatin-I (n = 6) had no effect on this neuron type. 3. On the other hand, achatin-I (n = 10) and [delta ZPhe2]-achatin-I (n = 10), ejected by brief pressure, produced an Iin on v-RCDN. The Iin values were 0.85 +/- 0.07 nA for achatin-I and 0.48 +/- 0.05 nA (p < 0.01, compared with that of achatin-I by Student's t-test for paired data) for [delta ZPhe2]achatin-I. The intervals between the compound ejection and the Iin peak were 5.95 +/- 0.33 s for achatin-I and 8.70 +/- 0.81 s (p < 0.05, compared with that of achatin-I) for [delta ZPhe2]achatin-I. [Aib2]achatin-I (n = 10) had no effect on this neuron type.
Gen Pharmacol 1997 Feb
PMID:Synthesis of achatin-I (Gly-D-Phe-L-Ala-L-Asp) analogs having dehydrophenylalanine or aminoisobutyric acid residue at position 2, and their effects on Achatina giant neurons. 901 5

Changes in adrenal hormones during the complete developmental cycle from egg to juvenile were investigated in the amphibian Xenopus laevis. Whole-body concentrations of the adrenal steroids corticosterone (B), and aldosterone (Aldo) were determined by radioimmunoassay and those of the adrenal catecholamines epinephrine (E), norepinephrine (NE), and dopamine (D) were determined by HPLC. In addition, the catecholamine-synthesizing enzymes tyrosine hydroxylase, dopamine beta-hydroxylase, and phenylethanolamine N-methyltransferase were immunocytochemically localized for the characterization of chromaffin adrenal cells. B and Aldo were not detectable in the whole body before hatching. B levels rose earlier than Aldo levels from stage 36 onward. B had already peaked at stage 46, whereas the largest amounts of Aldo were found at stage 54. After peaking, both steroids decreased gradually to 2.7 +/- 0.62 (B) and 0.4 +/- 0.1 (Aldo) ng/g body wt (mean +/- SEM, n = 10) in juvenile animals. E, NE, and D were detected just after hatching, when E and D showed an early peak at stage 40. E and NE increased moderately during development and demonstrated a sharp increase at the end of metamorphosis from stages 62 onward to 14.4 +/- 1.7 (E) and 34.1 +/- 4.67 (NE) ng/g body wt (mean +/- SEM, n = 6). Interestingly, D levels had a distinct pattern, because concentrations of D remained lower than those of NE and E over nearly the complete development, but showed a dramatic rise during the latest stages, reaching 707 +/- 54 ng/g body wt in juveniles. This dramatic shift in catecholamine levels was confirmed by immunocytochemistry in parallel. A large increase in chromaffin cells labeled with tyrosine hydroxylase immunoreactivity occurred in the latest developmental stages. The catabolic rates for all catecholamines in vivo were similar, which indicates that the different levels are due to various rates of synthesis. Thus, adrenal corticosteroids as well as catecholamines may have regulatory effects during premetamorphosis and metamorphic climax.
Gen Comp Endocrinol 1997 Dec
PMID:Stage-dependent changes in adrenal steroids and catecholamines during development in Xenopus laevis. 940 18

A spot confocal microscope based on an argon ion laser was used to make measurements of cytoplasmic calcium concentration (Ca2+i) from the outer segment of an isolated rod loaded with the fluorescent calcium indicator fluo-3 during simultaneous suction pipette recording of the photoresponse. The decline in fluo-3 fluorescence from a rod exposed to saturating illumination was best fitted by two exponentials of approximately equal amplitude with time constants of 260 and 2,200 ms. Calibration of fluo-3 fluorescence in situ yielded Ca2+i estimates of 670 +/- 250 nM in a dark-adapted rod and 30 +/- 10 nM during response saturation after exposure to bright light (mean +/- SD). The resting level of Ca2+i was significantly reduced after bleaching by the laser spot, peak fluo-3 fluorescence falling to 56 +/- 5% (SEM, n = 9) of its value in the dark-adapted rod. Regeneration of the photopigment with exogenous 11-cis-retinal restored peak fluo-3 fluorescence to a value not significantly different from that originally measured in darkness, indicating restoration of the dark-adapted level of Ca2+i. These results are consistent with the notion that sustained activation of the transduction cascade by bleached pigment produces a sustained decrease in rod outer segment Ca2+i, which may be responsible for the bleach-induced adaptation of the kinetics and sensitivity of the photoresponse.
J Gen Physiol 1998 Jan
PMID:Bleached pigment produces a maintained decrease in outer segment Ca2+ in salamander rods. 941 34

Vital bleaching of teeth is, increasingly, a popular esthetic desire. Bleaching agents are provided in over-the-counter as well as dental office bleaching kits. However, the effect of the bleaching agents on the enamel surface is not fully understood, and cautions approaches to their use are not usually explained to patients. In this study, an in vivo exposure of bleaching agents is used to evaluate the short and long-term effect on the enamel surface; the results are demonstrated by scanning with an electron microscope. Exposure to the bleaching agents for 14 days created an alteration of the enamel surface and caused exposure of the enamel prisms. Moreover, a 21- to 90-day post-exposure SEM evaluation demonstrated alteration of the surface enamel, indicating exposure of the enamel prismatic layer, frequently to the depth of the enamel rods and possibly the dentin.
Gen Dent
PMID:A scanning electron microscope study of the long-term effect of bleaching agents on the enamel surface in vivo. 966 68

The effects of turgor pressure-induced membrane tension on junctional coupling of Hensen cell isolates from the inner ear were evaluated by input capacitance or transjunctional conductance measurement techniques. Turgor pressure was altered by changing either pipette pressure or the osmolarities of extracellular solutions. Both positive pipette pressure and extracellular applications of hypotonic solutions, which caused cell size to concomitantly increase, uncoupled the cells as indicated by reduced input capacitance and transjunctional conductance. These changes were, in many cases, reversible and repeatable. Intracellular application of 50 microM H-7, a broad-based protein kinase inhibitor, and 10 mM BAPTA did not block the uncoupling effect of positive turgor pressure on inner ear gap junctions. The transjunctional conductance at a holding potential of -80 mV was 53.6 +/- 5.8 nS (mean +/- SEM, n = 9) and decreased approximately 40% at a turgor pressure of 1.41 +/- 0.05 kPa. Considering the coincident kinetics of cell deformation and uncoupling, we speculate that mechanical forces work directly on gap junctions of the inner ear. These results suggest that pathologies that induce imbalances in cochlear osmotic pressure regulation may compromise normal cochlear homeostasis.
J Gen Physiol 1998 Oct
PMID:Effect of membrane tension on gap junctional conductance of supporting cells in Corti's organ. 975 63

Using patch voltage-clamp techniques, we find there are two components to the voltage-gated potassium current (IKv) in rat brown adipocytes. The components differ in their gating and responses to purinergic stimulation, but not their pharmacology. IKv-A recovers from inactivation at physiological membrane potentials, while IKv-B inactivation recovers at more negative potentials. Both currents are >90% blocked by similar concentrations of quinine and tetraethylammonium, but not by beta-dendrotoxin, charybdotoxin, or apamin. The two current components are differentially modulated by extracellular ATP. ATP shifts the voltage dependence of IKv-A inactivation negative by 38 +/- 5 mV (n = 35, +/-SEM) and shifts activation by -14 +/- 2 mV in whole-cell experiments. ATP did not affect the steady state inactivation voltage dependence of IKv-B, but did apparently convert IKv-A into IKv-B. The pharmacology of the inactivation shift is consistent with mediation by a P2 purinergic receptor. Purinergic stimulation of perforated-patch clamped cells causes hyperpolarizing shifts in the window current of IKv-A by shifting inactivation -18 +/- 4 mV and activation -7 +/- 2 mV (n = 16). Since perforated-patch recordings will most closely resemble in vivo cell responses, this ATP-induced shift in the window current may facilitate IKv activation when the cell depolarizes. IKv activity is necessary for the proliferation and differentiation of brown adipocytes in culture (Pappone, P.A., and S.I. Ortiz-Miranda. 1993. Am. J. Physiol. 264:C1014-C1019) so purinergic modulation of IKv may be important in altering adipocyte growth and development.
J Gen Physiol 1999 Jan
PMID:P2 receptor modulation of voltage-gated potassium currents in Brown adipocytes. 987 93

Simultaneous measurements of photocurrent and outer segment Ca2+ were made from isolated salamander cone photoreceptors. While recording the photocurrent from the inner segment, which was drawn into a suction pipette, a laser spot confocal technique was employed to evoke fluorescence from the outer segment of a cone loaded with the Ca2+ indicator fluo-3. When a dark-adapted cone was exposed to the intense illumination of the laser, the circulating current was completely suppressed and fluo-3 fluorescence rapidly declined. In the more numerous red-sensitive cones this light-induced decay in fluo-3 fluorescence was best fitted as the sum of two decaying exponentials with time constants of 43 +/- 2.4 and 640 +/- 55 ms (mean +/- SEM, n = 25) and unequal amplitudes: the faster component was 1.7-fold larger than the slower. In blue-sensitive cones, the decay in fluorescence was slower, with time constants of 140 +/- 30 and 1,400 +/- 300 ms, and nearly equal amplitudes. Calibration of fluo-3 fluorescence in situ from red-sensitive cones allowed the calculation of the free-Ca2+ concentration, yielding values of 410 +/- 37 nM in the dark-adapted outer segment and 5.5 +/- 2.4 nM after saturating illumination (mean +/- SEM, n = 8). Photopigment bleaching by the laser resulted in a considerable reduction in light sensitivity and a maintained decrease in outer segment Ca2+ concentration. When the photopigment was regenerated by applying exogenous 11-cis-retinal, both the light sensitivity and fluo-3 fluorescence recovered rapidly to near dark-adapted levels. Regeneration of the photopigment allowed repeated measurements of fluo-3 fluorescence to be made from a single red-sensitive cone during adaptation to steady light over a range of intensities. These measurements demonstrated that the outer segment Ca2+ concentration declines in a graded manner during adaptation to background light, varying linearly with the magnitude of the circulating current.
J Gen Physiol 1999 Feb
PMID:Light-dependent changes in outer segment free-Ca2+ concentration in salamander cone photoreceptors. 992 24

In the experiments here, the time- and voltage-dependent properties of the Ca2+-independent, depolarization-activated K+ currents in adult mouse ventricular myocytes were characterized in detail. In the majority (65 of 72, approximately 90%) of cells dispersed from the ventricles, analysis of the decay phases of the outward currents revealed three distinct K+ current components: a rapidly inactivating, transient outward K+ current, Ito,f (mean +/- SEM taudecay = 85 +/- 2 ms); a slowly (mean +/- SEM taudecay = 1,162 +/- 29 ms) inactivating K+ current, IK,slow; and a non inactivating, steady state current, Iss. In a small subset (7 of 72, approximately 10%) of cells, Ito,f was absent and a slowly inactivating (mean +/- SEM taudecay = 196 +/- 7 ms) transient outward current, referred to as Ito,s, was identified; the densities and properties of IK,slow and Iss in Ito,s-expressing cells are indistinguishable from the corresponding currents in cells with Ito,f. Microdissection techniques were used to remove tissue pieces from the left ventricular apex and from the ventricular septum to allow the hypothesis that there are regional differences in Ito,f and Ito,s expression to be tested directly. Electrophysiological recordings revealed that all cells isolated from the apex express Ito,f (n = 35); Ito,s is not detected in these cells (n = 35). In the septum, by contrast, all of the cells express Ito,s (n = 28) and in the majority (22 of 28, 80%) of cells, Ito,f is also present. The density of Ito,f (mean +/- SEM at +40 mV = 6.8 +/- 0.5 pA/pF, n = 22) in septum cells, however, is significantly (P < 0.001) lower than Ito,f density in cells from the apex (mean +/- SEM at +40 mV = 34.6 +/- 2.6 pA/pF, n = 35). In addition to differences in inactivation kinetics, Ito,f, Ito,s, and IK,slow display distinct rates of recovery (from inactivation), as well as differential sensitivities to 4-aminopyridine (4-AP), tetraethylammonium (TEA), and Heteropoda toxin-3. IK,slow, for example, is blocked selectively by low (10-50 microM) concentrations of 4-AP and by (>/=25 mM) TEA. Although both Ito,f and Ito,s are blocked by high (>100 microM) 4-AP concentrations and are relatively insensitive to TEA, Ito,f is selectively blocked by nanomolar concentrations of Heteropoda toxin-3, and Ito,s (as well as IK,slow and Iss) is unaffected. Iss is partially blocked by high concentrations of 4-AP or TEA. The functional implications of the distinct properties and expression patterns of Ito,f and Ito,s, as well as the likely molecular correlates of these (and the IK,slow and Iss) currents, are discussed.
J Gen Physiol 1999 May
PMID:Four kinetically distinct depolarization-activated K+ currents in adult mouse ventricular myocytes. 1022 81

Using the whole-cell mode of the patch-clamp technique, we recorded action potentials, voltage-activated cationic currents, and inward currents in response to water-soluble and volatile odorants from receptor neurons in the lateral diverticulum (water nose) of the olfactory sensory epithelium of Xenopus laevis. The resting membrane potential was -46.5 +/- 1.2 mV (mean +/- SEM, n = 68), and a current injection of 1-3 pA induced overshooting action potentials. Under voltage-clamp conditions, a voltage-dependent Na+ inward current, a sustained outward K+ current, and a Ca2+-activated K+ current were identified. Application of an amino acid cocktail induced inward currents in 32 of 238 olfactory neurons in the lateral diverticulum under voltage-clamp conditions. Application of volatile odorant cocktails also induced current responses in 23 of 238 olfactory neurons. These results suggest that the olfactory neurons respond to both water-soluble and volatile odorants. The application of alanine or arginine induced inward currents in a dose-dependent manner. More than 50% of the single olfactory neurons responded to multiple types of amino acids, including acidic, neutral, and basic amino acids applied at 100 microM or 1 mM. These results suggest that olfactory neurons in the lateral diverticulum have receptors for amino acids and volatile odorants.
J Gen Physiol 1999 Jul
PMID:Responses of Xenopus laevis water nose to water-soluble and volatile odorants. 1039 94

This study investigated whether genetically lean and fat sheep displayed differences in insulin and glucose statuses. Lean genotype sheep had significantly (P < 0.05) greater basal glucose concentrations than fat genotype sheep (4.78 versus 4.52, SED = 0. 104 mmol/l), although basal plasma insulin was not significantly different (mean 304, SEM = 37.3 pmol/l) between the genotypes. During glucose tolerance tests (GTT), carried out at 4 levels of injection: 0, 0.28, 1.39 or 2.78 mmol glucose/kg liveweight, the area under the plasma insulin curve was significantly (P < 0.05) greater for fat than lean genotype sheep, although there were no differences in any glucose parameters. There were no significant differences between genotypes in insulin or glucose concentrations during or following glucose infusion (GINF) experiments at 0, 0.09, 0.46 or 0.93 mmol glucose/kg live-weight/h over 3 hours. Elevated plasma insulin concentrations after a glucose tolerance test are concluded to be associated with increased fatness in this genetically selected line of sheep. However, the differences in insulin and glucose levels between the lean and fat genotype sheep are minor, relative to the differences in carcass composition.
Gen Comp Endocrinol 1999 Oct
PMID:Plasma glucose and insulin levels in genetically lean and fat sheep. 1052 66


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>