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At least 433 records · Page 24Linked to original sources

Dynamic imaging of free cytosolic ATP concentration during fuel sensing by rat hypothalamic neurones: evidence for ATP-independent control of ATP-sensitive K(+) channels.

Glucose-responsive (GR) neurons from hypothalamic nuclei are implicated in the regulation of feeding and satiety. To determine the role of intracellular ATP in the closure of ATP-sensitive K(+) (K(ATP)) channels in these cells and associated glia, the cytosolic ATP concentration ([ATP](c)) was monitored in vivo using adenoviral-driven expression of recombinant targeted luciferases and bioluminescence imaging. Arguing against a role for ATP in the closure of K(ATP) channels in GR neurons, glucose (3 or 15 mM) caused no detectable increase in [ATP](c), monitored with cytosolic luciferase, and only a small decrease in the concentration of ATP immediately beneath the plasma membrane, monitored with a SNAP25-luciferase fusion protein. In contrast to hypothalamic neurons, hypothalamic glia responded to glucose (3 and 15 mM) with a significant increase in [ATP](c). Both neurons and glia from the cerebellum, a glucose-unresponsive region of the brain, responded robustly to 3 or 15 mM glucose with increases in [ATP](c). Further implicating an ATP-independent mechanism of K(ATP) channel closure in hypothalamic neurons, removal of extracellular glucose (10 mM) suppressed the electrical activity of GR neurons in the presence of a fixed, high concentration (3 mM) of intracellular ATP. Neurons from both brain regions responded to 5 mM lactate (but not pyruvate) with an oligomycin-sensitive increase in [ATP](c). High levels of the plasma membrane lactate-monocarboxylate transporter, MCT1, were found in both cell types, and exogenous lactate efficiently closed K(ATP) channels in GR neurons. These data suggest that (1) ATP-independent intracellular signalling mechanisms lead to the stimulation of hypothalamic neurons by glucose, and (2) these effects may be potentiated in vivo by the release of lactate from neighbouring glial cells.

Adenosine Triphosphate↗

A5 noradrenergic neurons and the carotid sympathetic chemoreflex.

Inhibition of neural activity in the caudal ventrolateral pons (A5 area) by microinjection of muscimol (Mus) attenuates (-65%) the carotid sympathetic chemoreflex (SChR) without altering the concomitant activation of the phrenic nerve (PND). The present study, performed in urethan-anesthetized rats, explores the possibility that activation of the noradrenergic (NE) neurons of the A5 area is involved in the SChR. The NE neuron-selective toxin 6-hydroxydopamine (6-OHDA) was microinjected bilaterally into the spinal cord at T2 level (4 micrograms). This dose reduced the SChR by 55% (n = 5) 90 min after injection, while 0.4 microgram of 6-OHDA produced no effect (n = 5). In seven rats that had received 250 micrograms 6-OHDA intracisternally 2 wk before, Mus injections into the A5 area failed to attenuate the SChR. These rats also had a lower resting mean arterial pressure than controls (97 vs. 112 mmHg). Spinal intrathecal injection of alpha-adrenergic receptor antagonists (prazosin, 10 and 20 micrograms) or phentolamine (20 and 40 micrograms) attenuated resting sympathetic nerve discharge (SND) and SChR in a roughly proportional manner (25-40%); the beta-adrenergic antagonist nadolol (10 and 20 microgram(s) intrathecally) attenuated the SChR selectively but modestly (-10%). The results are generally compatible with the hypothesis that A5 NE neurons and particularly their spinal cord projection could play a facilitating role in the SChR. However, clear evidence that A5 cells contribute selectively to sympathoactivation during chemoreceptor stimulation by releasing NE in the spinal cord could not be obtained.

Animals↗

Amine-containing cells of the lung.

In many vertebrates, including mammals, there are amine-containing cells in the walls of the airways and the lungs. Despite a plethora of names for these cells, there is a general agreement about their structure. They occur singly or in groups (NEBs), but the functional distinction between the two types of distribution is uncertain. In spite of ultrastructural similarities, the cells may be physiologically heterogenous. The cells are characterised by their staining characteristics and content of electron-dense-core vesicles, which are believed to contain a biogenic amine. They also have additional cytoplasmic features common to other sensory paraganglia. They may be more numerous in certain species and also in the neonate. The NEBs may be innervated with afferent and/or efferent nerves, though physiological evidence of their innervation is scanty. The most popular hypothesis is that they can be stimulated by hypoxia to release mediators or to induce reflex activity. In the healthy animal, the amine-cells may control local ventilation/perfusion (V/Q) ratios via an action on the pulmonary vasculature. In disease, they may cause pulmonary hypertension. They can also give rise to three forms of tumour. Their full significance has yet to be established.

APUD Cells↗

Release of 5-hydroxytryptamine by hypoxia from epithelioid cells of chicken thoracic aorta.

Epithelioid cells in the chicken thoracic aorta are shown to contain 5-hydroxytryptamine (5-HT) in immunocytochemical studies. To determine whether these cells act as chemoreceptors, as do type I cells of the carotid body, we examined the effects of hypoxia and acidosis on the release of 5-HT from the chicken thoracic aorta. Hypoxia caused the output of 5-HT in incubation medium. A reduction of pH to 6.8 failed to evoke 5-HT release. The response to hypoxia was inhibited by the removal of extracellular Ca2+ and by nifedipine and omega-conotoxin GVIA. These results suggest that epithelioid cells in the chicken thoracic aorta are chemoreceptors which sense a decrease in PO2 and then release 5-HT by Ca2+ influx through voltage-dependent L- and N-type Ca2+ channels. The epithelioid cells in the chicken aorta may be a useful model for pharmacological and physiological studies of 5-HT-containing cells.

Animals↗

Effects of renal receptor stimulation on neurons within the ventrolateral medulla of the cat.

Experiments were performed to determine if activation of renal receptors by occlusion of the renal artery, renal vein, or ureter would alter activity of cells within the ventrolateral medulla of the cat. Extracellular unit recordings were obtained from 195 cells located within the rostral ventrolateral medulla of 90 alpha-chloralose-anesthetized cats. Fifty-five of 195 cells (28.2%) tested for responses to renal receptor activation responded to at least one of the occlusions. Occlusion of the ureter increased the activity of 25 cells from 9.7 +/- 3.7 to 23.0 +/- 6.5 impulses/s and decreased the activity of 5 cells from 11.9 +/- 3.6 to 3.5 +/- 1.2 impulses/s. Occlusion of the renal vein increased the activity of seven cells from 7.5 +/- 3.3 to 22.3 +/- 7.3 impulses/s and decreased the activity of six cells from 13.8 +/- 3.8 to 4.1 +/- 2.0 impulses/s. Renal artery occlusion elicited solely excitatory responses from 43 cells. Thirty-one of the 43 cells increased their activity within 0-3 s of the onset of renal artery occlusion from 4.1 +/- 0.8 to 12.6 +/- 1.2 impulses/s. Renal artery occlusion increased the activity of 10 out of 43 cells with a mean latency of 26.1 +/- 6.5 s from 8.3 +/- 2.5 to 29.6 +/- 9.3 impulses/s. Twenty-four of the 55 (43.6%) responders were responsive to two or more forms of renal receptor activation. These results demonstrate that activation of renal mechanoreceptors and chemoreceptors affects cells within the ventrolateral medulla of the cat.(ABSTRACT TRUNCATED AT 250 WORDS)

Adaptation, Physiological↗

Angiotensin AT1 receptor-mediated excitation of rat carotid body chemoreceptor afferent activity.

1. A high density of angiotensin II receptors was observed in the rat carotid body by in vitro autoradiography employing 125I-[Sar1, Ile8]-angiotensin II as radioligand. Displacement studies demonstrated that the receptors were of the AT1 subtype. 2. The binding pattern indicated that the AT1 receptors occurred over clumps of glomus cells, the principal chemoreceptor cell of the carotid body. Selective lesions of the sympathetic or afferent innervation of the carotid body had little effect on the density of receptor binding, demonstrating that the majority of AT1 receptors were intrinsic to the glomus cells. 3. To determine the direct effect of angiotensin II on chemoreceptor function, without the confounding effects of the vasoconstrictor action of angiotensin II, carotid sinus nerve activity was recorded from the isolated carotid body in vitro. The carotid body was superfused with Tyrode solution saturated with carbogen (95 % O2, 5 % CO2), maintained at 36 C, and multi-unit nerve activity recorded with a suction electrode. 4. Angiotensin II elicited a dose-dependent excitation of carotid sinus nerve activity (maximum increase of 36 +/- 11 % with 10 nM angiotensin II) with a threshold concentration of 1 nM. The response was blocked by the addition of an AT1 receptor antagonist, losartan (1 microM), but not by the addition of an AT2 receptor antagonist, PD123319 (1 microM). 5. In approximately 50 % of experiments the excitation was preceded by an inhibition of activity (maximum decrease of 24 +/- 8 % with 10 nM angiotensin II). This inhibitory response was markedly attenuated by losartan but not affected by PD123319. 6. These observations demonstrate that angiotensin II, acting through AT1 receptors located on glomus cells in the carotid body, can directly alter carotid chemoreceptor afferent activity. This provides a means whereby humoral information about fluid and electrolyte homeostasis might influence control of cardiorespiratory function.

1-Sarcosine-8-Isoleucine Angiotensin II↗

Receptors for N-acetylated sugars may stimulate adenylate cyclase to sensitize and tune mechanoreceptors involved in triggering nematocyst discharge.

In fishing tentacles of sea anemones, cnidocyte/supporting cell complexes (CSCCs) trigger the discharge of nematocysts following stimulation by swimming prey of specific mechanoreceptors and chemoreceptors located on the supporting cells. Two types of mechanoreceptors have been identified: a contact-sensitive mechanoreceptor (CSM), and a vibration-sensitive mechanoreceptor (VSM). The CSMs become predisposed to initiate nematocyst discharge into static (i.e., nonvibrating) test probes in the presence of submicromolar free and conjugated N-acetylated sugars, a process referred to as sensitization. In seawater, the VSMs cause maximal discharge in response to test probes vibrating at 30, 50-55, and 75 Hz, whereas in the presence of submicromolar N-acetylated sugars the VSMs cause maximal discharge into test probes vibrating at 5, 15, 30, and 40 Hz, a process referred to as tuning. Tuning of the VSMs is accompanied by elongation of the stereocilium bundles comprising the VSMs. We report that dibutyryl cyclic-AMP sensitizes CSMs and tunes VSMs to the lower frequencies of 5, 15, 30, and 40 Hz, while cyclic-AMP has no such effects. Endogenous adenylate cyclase activity at the apical plasma membrane of the supporting cells is detectable by cytochemical methods in the presence of N-acetylated sugars but not in seawater alone. By activating adenylate cyclase with L858051, an analogue of forskolin, or by activating the stimulatory form of G proteins (Gs) with cholera toxin, CSCCs are induced to sensitize CSMs and to tune VSMs to the lower frequencies of 5, 15, 30, and 40 Hz. Caged GTP-gamma S also sensitizes CSMs but tunes VSMs to 5, 15, 30, 40, 55, 65, and 75 Hz, suggesting that VSM tuning may be regulated both by Gs and inhibitory G-proteins. Together, these results implicate cAMP as the second messenger for activated supporting cell chemoreceptors involved in sensitizing the CSMs and tuning the VSMs to lower frequencies.

Acetylglucosamine↗

The structure of teleost epidermis with special reference to new qualitative and quantitative data from the guppy, Poecilia reticulata Peters.

Scales from the midlateral body region of adult male guppies, Poecilia reticulata Peters, were investigated morphometrically by light and electron microscopy. The epidermis consists of one superficial layer and, in general, two basal layers of filament-containing cells and a number of mucous cells. There are scattered chemosensory cells and unmyelinated nerve fibres. Superficial cells are flattened and form apical ridges in a fingerprint-like arrangement. The volume density of mitochondria, granular endoplasmic reticulum, and numerical density of dictyosomes are higher in superficial cells than in basal cells. The superficial cells are secretorily active. Small electron dense vesicles are transported from the dictyosomes to the body surface and yield the glycocalyx material, which is not identical with the slime produced by the mucous cells.

Animals↗