Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01189 (beta-endorphin)
 21,003 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. In cultured rat locus coeruleus neurons, somatostatin or met-enkephalin induces an inwardly rectifying K+ conductance. This inward rectifier was analyzed at the single-channel level. 2. Using the inside-out patch-clamp, guanosine 5'-triphosphate (GTP) application to the cytoplasmic side in the presence of somatostatin or met-enkephalin in the pipette produced a large increase in channel activity, which disappeared on switching from GTP to guanosine 5'-diphosphate. 3. The unitary conductance was approximately 30 pS at -95 mV with an extracellular K+ concentration of 156 mM and an intracellular K+ concentration of 124 mM at 23 degrees C. The channel showed burst behavior, and the closed time histogram was fit by two exponentials, with the fast time constant being 0.4 ms. The burst time histogram was also fit by two exponentials, with time constants of 0.24 and 2.0 ms (at 10 nM somatostatin). When the somatostatin concentration was changed from 500 to 1 nM, the kinetic behavior of the channel did not change, except that the open probability of the patch was decreased. 4. The current-voltage relation of the unitary channel current showed inward rectification. The reversal potential coincided with the K+ equilibrium potential, and it shifted according to a change in the K+ equilibrium potential. 5. In the presence of external somatostatin, the application of guanosine 5'-O-(3-thiotriphosphate) to the cytoplasmic side induced an irreversible activation of this channel. 6. These results indicate that this K+ channel is the microscopic counterpart of the somatostatin- or met-enkephalin-induced inwardly rectifying K+ current in whole cell recording, and that the channel is activated by a G protein without a diffusible second messenger. Thus this channel is identified as a neuronal G-protein-coupled inward rectifier K+ channel. 7. Analysis of the burst behavior, based on a close-close-open kinetic model, revealed that there are at least four states in the K+ channel, a short gap, a longer closing, a short opening, and a long opening, and that the neuronal inward rectifier is activated at faster rates than the atrial inward rectifier.
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PMID:Single-channel properties of a G-protein-coupled inward rectifier potassium channel in brain neurons. 882 60

Bovine adrenal zona fasciculata cells express a novel K+ current (IAC) that sets the resting potential while it couples adrenocorticotropin and angiotensin II receptors to membrane depolarization and cortisol secretion. IAC is distinctive among K+ channels both in its activation by ATP and its inhibition by cyclic AMP. Whole-cell and single-channel patch-clamp recording was used to establish a pharmacological profile of IAC K+ channels. IAC was blocked by antagonists of cyclic nucleotide-gated channels, including the diphenylbutylpiperidine (DPBP) antipsychotic pimozide and l-cis-diltiazem. Other DPBPs, including penfluridol and fluspirilene, also potently inhibited this channel. The inhibition of IAC by DPBPs was selective because 200-fold higher concentrations of penfluridol were required to inhibit voltage-gated IA K+ channels in adrenal zona fasciculata cells. Standard K+ channel antagonists blocked IAC at concentrations 100- to 100,000-fold higher than the DPBPs. IAC channels were also inhibited by the sulfonylureas glyburide and tolbutamide but at concentrations higher than those that typically block ATP-sensitive inward rectifier K+ channels. Overall, the relative order of potency and associated IC50 values for IAC antagonists were as follows: penfluridol (0.187 microM) > fluspirilene (0.232 microM) > pimozide (0.354 microM) >> l-cis-diltiazem (24.9 microM) approximately quinidine (24.1 microM) > bupivacaine (113.2 microM) > tolbutamide (784.4 microM) > BaCl2 (1027 microM) > 4-aminopyridine (2750 microM) > tetraethylammonium (24,270 microM). IAC channels are unique in combining the pharmacological properties of K+-selective channels with those of cyclic nucleotide-gated cation channels. The potent block of IAC channels identifies DPBPs as a new class of K+ channel antagonists and suggests additional targets for these neuroleptics in the central nervous system.
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PMID:Dual pharmacological properties of a cyclic AMP-sensitive potassium channel. 1038 86

The rostral portion of the nucleus of the solitary tract (rNST) is an obligatory relay for gustatory afferent input on its way to the forebrain. Previous studies have demonstrated excitation of rNTS neurons by glutamate and substance P and inhibition by gamma-aminobutyric acid (GABA) and met-enkephalin (ENK). Despite the existence of cholinergic neurons and putative terminals within the rNTS, there are no data on the effects of acetylcholine (ACh) on rNTS processing. Here, we use patch-clamp recording of rNTS neurons in vitro to examine ACh-mediated responses and voltage-gated conductances in these cells. Results revealed (1) intrinsic voltage-gated inhibition via activation of voltage-gated potassium A-channels (I(A)), found almost exclusively in the medial rNTS, and hyperpolarization-activated potassium/sodium channels (I(h)), found more frequently in the lateral rNST; and (2) ligand-gated inhibition via activation of muscarinic m2 ACh receptors (mAChRs) linked to inward rectifier potassium channels (K(ir)) evenly distributed throughout the rNTS, a mechanism dependent on cholinergic inputs. Muscarinic responses were blocked by AFDX-116, a selective m2 mAChR antagonist, and by BaCl2, an antagonist of K(ir) channels. In addition, many rNTS neurons exhibited excitation via alpha7 and non-alpha7 nicotinic AChRs. Non-alpha7 nAChRs, blocked by 10 microM mecamylamine, occurred more frequently in the lateral rNTS. In contrast, alpha7 nAChRs, blocked by 20 nM methyllcaconitine, were evenly distributed across the nucleus. As previously reported for voltage-activated conductances, none of these currents was related to neuronal morphology. These voltage- and ligand-dependent inhibitory mechanisms would be expected to contribute to the modulation of gustatory processing through the NST.
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PMID:Cholinergic modulation of neurons in the gustatory region of the nucleus of the solitary tract. 1654 41