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Biomedical subjects

I Hanbauer

Publications and source records attributed to I Hanbauer.

At least 19 recordsLinked to original sources
PubMed1992

K(+)-evoked dopamine release depends on a cytosolic Ca2+ pool regulated by N-type Ca2+ channels.

Membrane depolarization evoked by 25-40 mM K+ elicited an immediate increase of somatic and neuritic [Ca2+]i in cultured dopaminergic neurons as measured by digital fluorescence microscope imaging. The rise of neuritic [Ca2+]i was inhibited by N-type but not L-type Ca2+ channel blockers, while the rise of somatic [Ca2+]i was prevented by both L- and N-type Ca2+ channel blockers. Similarly, depolarization-induced [3H]dopamine release was selectively attenuated by N-type Ca2+ channel blockers. The present results suggest that [3H]dopamine release from mesencephalic neuronal cell cultures relates to a Ca(2+)-dependent mechanism regulated by N-type channels located in the vicinity of the exocytotic sites within neuritic processes.

Animals↗
PubMed1992

Role of nitric oxide in NMDA-evoked release of [3H]-dopamine from striatal slices.

Evidence that excitatory amino acids act via N-methyl-D-aspartate (NMDA) receptors to evoke the release of catecholamines from axonal terminals and synaptosomes has been used to argue for the presence of pre-synaptic NMDA receptors. NMDA receptor agonists also generate nitric oxide (NO) which rapidly diffuses through neural tissue. We find that exogenously applied NO evokes [3H]-dopamine release from cultured neurons. This release is not blocked by the NMDA antagonist MK-801 nor by tetrodotoxin. Both NG-nitroarginine which inhibits NO synthesis, and hemoglobin which binds extracellular NO, block NMDA-evoked [3H]-dopamine release from striatal slices. A major role of endogenously-synthesized NO may be to evoke neurotransmitter release in local volumes of neural tissue.

Animals↗
PubMed1991

Characterization of [3H]dopamine uptake sites and [3H]cocaine recognition sites in primary cultures of mesencephalic neurons during in vitro development.

[3H]Dopamine uptake and [3H]cocaine binding sites were studied in primary cultures of ventral mesencephalon from 14-day-old rat embryos. Specific binding sites for [3H]cocaine and [3H]mazindol were detected only in intact cell cultures of ventral mesencephalon, and were absent in sonicated, washed membranes prepared from these cell cultures. [3H]Cocaine was not taken up by the cells through an active transport process because [3H]cocaine binding occurred also at 4 degrees C. Moreover, the possibility of [3H]cocaine entering the cells by passive diffusion and ion trapping was also excluded because extensive washing failed to remove [3H]cocaine from the cells. [3H]Cocaine binding was reduced to 6% of control when cells were permeabilized with streptolysin O (0.2 U/ml, 5 min). Taken together, these results suggest that in cultured mesencephalic neurons, [3H]cocaine may enter the cell by passive diffusion and then be sequestered by a cytosolic compartment that is lost in the process of permeabilization or sonication and washing of membrane preparations. Permeabilization of cultured neurons failed to alter the storage of [3H]dopamine. When cells were permeabilized with streptolysin O (0.2 U/ml; 5 min) after [3H]dopamine was taken up, [3H]dopamine was retained by the cells and did not leak into the incubation medium, indicating that [3H]dopamine was stored in sites that could not pass through the perforated membranes. In contrast, [3H]dopamine uptake into already permeabilized cells was reduced by 33%, suggesting that a cytosolic protein that had leaked out may play a functional role in the uptake process. In contrast to striatal membrane preparations of adult rats, [3H]cocaine binding in intact mesencephalic cell cultures was Na+ independent.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Modulation of calcium channels in cardiac and neuronal cells by an endogenous peptide.

Calcium channels mediate the generation of action potentials, pacemaking, excitation-contraction coupling, and secretion and signal integration in muscle, secretory, and neuronal cells. The physiological regulation of the L-type calcium channel is thought to be mediated primarily by guanine nucleotide-binding proteins (G proteins). A low molecular weight endogenous peptide has been isolated and purified from rat brain. This peptide regulates up and down the cardiac and neuronal calcium channels, respectively. In cardiac myocytes, the peptide-induced enhancement of the L-type calcium current had a slow onset (half-time approximately 75 seconds), occurred via a G protein-independent mechanism, and could not be inhibited by alpha 1-adrenergic, beta-adrenergic, or angiotensin II blockers. In neuronal cells, on the other hand, the negative effect had a rapid onset (half-time less than 500 milliseconds) and was observed on both T-type and L-type calcium channels.

Angiotensin II↗
PubMed1989

Evidence for the involvement of distinct voltage-sensitive calcium channels in the release of 3H-dopamine from primary cultures of mesencephalic neurons.

In ventral mesencephalic neurons cultured for five days the K+-evoked 3H-dopamine release is mediated through activation of N-type Ca2+ channels, while L- or T-type channels appear to be inactive. In contrast, veratridine-elicited release of 3H-dopamine that was attenuated by tetrodotoxin was not altered by N-, L-, nor T-type Ca2+ channel blockers.

Animals↗
PubMed1987

Evidence that [3H]forskolin binding in the substantia nigra is intrinsic to a striatal-nigral projection: an autoradiographic study of rat brain.

The neuronal localization of binding sites for the diterpene activator of adenylate cyclase, forskolin, has been determined. Kainic or ibotenic acid lesions were administered into the caudate-putamen or substantia nigra of Sprague-Dawley rats. The binding of 20 nM [3H]forskolin was examined autoradiographically and quantitated using computerized densitometry with tritium standards. Neurochemical lesions placed in the caudate-putamen markedly reduced [3H]forskolin binding in this structure and distal to the site of injection in the substantia nigra. Ibotenic acid lesions placed in the substantia nigra did not appreciably alter binding in the substantia nigra, caudate-putamen, nucleus accumbens or olfactory tubercle. These results indicate that 'forskolin-identified' adenylate cyclase in the substantia nigra is located in nerve terminals from the caudate-putamen. In addition, these sites are presumably located on cell bodies or interneurons in the caudate-putamen.

Adenylyl Cyclases↗
PubMed1987

Isolation from rat brain tissue of an inhibiting activity for dihydropyridine binding sites and voltage-dependent CA2+ uptake.

Nitrendipine binding-inhibitory activity was extracted and partially purified from rat brain. This preparation also decreased veratridine-stimulated Ca2+ uptake in cultured cerebellar granule cells. It failed to inhibit 3H-nitrendipine binding by sequestering Ca2+ that is required for the high affinity binding of nitrendipine. An allosteric modulation of nitrendipine recognition sites by this preparation is suggested.

Animals↗
PubMed1987

Effect of gamma-aminobutyric acidA receptor agonists and antagonists on the release of enkephalin-containing peptides from dog adrenal gland.

Chromaffin cells of the adrenal medulla are known to store and release catecholamines, Met5-enkephalin (ME)-like peptides and gamma-aminobutyric acid (GABA). The present study documents that stimulation of GABAA receptors located on chromaffin cell membranes of canine adrenal glands, eliciting depolarization of chromaffin cell membranes, modulates the responsiveness of chromaffin cells to splanchnic nerve stimulation. 4,5,6,7-Tetrahydroisoxazolo[5,4-c]pyridin-3-ol (0.143 mmol/2 ml/min), a selective GABAA receptor agonist infused into the aortic pouch, increases the release of ME-like peptides and catecholamines into the adrenal effluent blood. Prior infusion into the aortic pouch of the GABAA receptor blocker, bicuculline (0.05 mmol/2 ml/min), prevents the 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol-elicited release of both substances. A stoichiometric relationship exists between the release of both substances; 1 nmol/ml of plasma of catecholamines was coreleased with 2 pmol/ml of plasma of ME-like peptides. The chromatographic profile on a Sephadex G-75 column indicates that, after injection of 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol, various MW forms of ME-like peptides are released into the adrenal effluent blood. A similar profile for the release of ME-like peptides was obtained when electrical stimulation (10 V/6 Hz) of the splanchnic nerve was used as a stimulus. These data suggest that direct stimulation of GABAA receptors causes depolarization of chromaffin cell membranes by a burst of Cl- channel opening and triggers neurotransmitter release.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Medulla↗
PubMed1986

Evidence for a specific effect of BHT 920, an azepine derivative, on tyrosine hydroxylase in the dopaminergic system of the rat.

The effect of BHT 920, a putative presynaptic dopamine receptor agonist, on tyrosine hydroxylase was investigated in rats. The activity of the high affinity (BH4) form of striatal tyrosine hydroxylase was investigated dose-dependent manner in rats treated with BHT 920. This effect was pronounced in the dopaminergic system and was not observed to the same extent in the adrenal medulla. In vitro, BHT 920 had no effect upon striatal tyrosine hydroxylase activity. BHT 920 also did not affect either striatal adenylate cyclase activity or the extent of its stimulation by dopamine. The results concerning tyrosine hydroxylase were complemented by measurements of dopamine and DOPA in the striatal and the limbic system. The reduction in DOPA accumulation and in the high affinity form of tyrosine hydroxylase activity elicited by BHT 920 could be blocked by haloperidol, suggesting that BHT 920 may interact with the D2 dopamine receptor although a functional antagonism could not be ruled out. The present results suggest that BHT 920 may exert a specific effect upon tyrosine hydroxylase in dopaminergic nervous tissue which is not mediated by alpha 2-adrenoceptors.

Adenylyl Cyclases↗
PubMed1986

Lack of evidence for impaired dopamine receptor function in experimental hepatic coma in the rabbit.

In order to determine whether hepatic coma is associated with an altered sensitivity of the dopamine (DA) receptor in the brain, the activity of DA-sensitive adenylate cyclase was assayed in homogenates from the corpus striatum of normal rabbits and rabbits with galactosamine-induced fulminant hepatic failure by measuring cyclic adenosine monophosphate production from adenosine triphosphosphate radioimmunochemically. The kinetic properties of adenylate cyclase in control rabbits and rabbits with hepatic coma were similar (Km, 17 +/- 2.9 (S.E.M.) vs 20 +/- 6.4 mM; Vmax, 816 +/- 58 vs 1054 +/- 233 pmol/mg protein/5 min, respectively). Hepatic coma was not associated with any changes in the responses of the DA receptor-adenylate cyclase system to DA (maximum stimulation 60% vs 57%), sodium fluoride (maximum stimulation 104% vs 132%), or a D-2 DA receptor agonist (maximum inhibition 18% vs 12%). These findings make it unlikely that alterations of dopaminergic neurotransmission play an important role in the pathogenesis of hepatic coma.

Adenylyl Cyclases↗
PubMed1986

Evidence for a selective localization of voltage-sensitive Ca2+ channels in nerve cell bodies of corpus striatum.

Specific binding sites for [3H]nitrendipine, an organic Ca2+ channel antagonist, were abolished in crude synaptosomal membranes of kainic acid-lesioned caudate nuclei. In contrast, specific lesions of dopaminergic or serotonergic axon terminals in caudate nuclei failed to alter the density or the affinity of [3H]nitrendipine binding sites. In addition, the basal and veratridine-stimulated 45Ca2+ accumulations were greatly impaired in slices prepared from kainic acid-lesioned caudate nuclei. The veratridine-elicited accumulation of 45Ca2+ in control slices was attenuated by addition of tetrodotoxin in the incubation medium. The present data provide evidence that most of the [3H]nitrendipine binding sites and the voltage-dependent Ca2+ channels are located in intrinsic neurons or interneurons in caudate nucleus. In contrast, destruction of dopaminergic or serotonergic nerve terminals emanating from other brain areas and innervating the caudate nucleus failed to change the apparent Bmax value for [3H]nitrendipine binding.

5,7-Dihydroxytryptamine↗
PubMed1986

Intrinsic gamma aminobutyric acid receptors modulate the release of catecholamine from canine adrenal gland in situ.

Immunohistochemical analysis documented the presence of gamma-aminobutyric acid (GABA)-containing fibers and GABA-containing chromaffin cells in canine adrenal glands. A dense network of fibers was visualized at the boundary between medullary and cortical cells, and, in the medullary tissue, GABA-containing fibers surrounded chromaffin cells. Some of these fibers enter the adrenal medulla together with splanchnic cholinergic nerves. The functional role of the GABAergic system in the regulation of catecholamine release from adrenal chromaffin cells was studied in canine adrenal glands in situ, using an autoperfusion system for the adrenal gland that was designed to eliminate indirect central effects of drugs or their metabolites on catecholamine release. The present study documents that GABA modulates the spontaneous release of catecholamines and the release elicited by electrical stimulation of the splanchnic nerve. GABAA receptor agonists such as THIP or muscimol increased the catecholamine content in adrenal effluent blood, whereas bicuculline (0.05 mmol/2 ml min-1), a GABAA receptor antagonist, reduced it. Baclofen (0.094 mmol/2 ml min-1), a GABAB receptor agonist, failed to alter the catecholamine content in adrenal effluent blood. The increased release of catecholamines elicited by 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3[2H]-one (THIP; 0.143 mmol/2 ml min-1) was prevented by bicuculline (0.05 mmol/2 ml min-1) but not by hexamethonium (2.48 mmol/2 ml min-1) or naloxone (0.122 mmol/2 ml min-1). Furthermore, denervation of the adrenal glands failed to prevent the THIP-elicited release of catecholamines.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Medulla↗
PubMed1986

Participation of GABA/benzodiazepine receptor system in the adrenal chromaffin cell function.

Histochemical studies have shown that GABA-containing nerve terminals impinge upon the chromaffin cells and that approximately 40% of the chromaffin cells store and release GABA. These observations are compatible with the possibility that GABA receptors located on specific populations of chromaffin cells can be activated either by GABA released from nerve terminals or by GABA released from adjacent chromaffin cells. Indeed, experiments with bicuculline indicate that in bovine chromaffin cells in culture and in the adrenal medulla of dog in vivo, the secretion of CA and opioid peptides mediated by activation of nicotinic receptors is under tonic control of GABA. In a series of pharmacological experiments in dog, we have shown that appropriate doses of GABA or other GABA-mimetic drugs release CA into the circulation. This release, comparable in its magnitude to that obtained by injecting a full pharmacological dose of carbamylcholine or by maximally efficient electrical stimulation of the splanchnic nerve, was not blocked by hexamethonium, naloxone or splanchnicotomy, but instead, was prevented by treatment with bicuculline methiodide. These data suggest that GABA-induced CA release is not the consequences of activation of transynaptic mechanisms involving either acetylcholine, enkephalin or GABA acting at the GABAB receptors, but rather the result of stimulation of GABAA receptors linked to C1- channels located on the membranes of the adrenal chromaffin cells. Because the administration of GABA was found to induce depolarization in autonomic mammalian ganglia in electrophysiological studies (DeGroat, 1970), we propose that the GABA-mediated release of CA from dog adrenal medulla is the consequence of chromaffin cell depolarization.(ABSTRACT TRUNCATED AT 250 WORDS)

4-Aminobutyrate Transaminase↗