Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027960 (mole)
 21,279 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. The amounts of endogenous serotonin (5-HT) released into the medium by the cerebro-buccal ganglionic ring of Aplysia californica incubated in artificial sea water (ASW) were measured. The rate of spontaneous 5-HT release varied between 0.4 and 1.2 p-mole per hour, which is less than 1% of the total 5-HT present in this preparation.2. Direct stimulation of the ordinarily silent 5-HT-containing giant cerebral neurones resulted in a 80-100% increase of the 5-HT released, but only when the 5-HT uptake was blocked by chlorimipramine (1-10 muM).3. High K(+) media (50 mM) also caused a significant increase in the amount of 5-HT released from the preparation provided that chlorimipramine (1-10 muM) was present in the incubation fluid.4. Co(2+) ions (10-30 mM) added to the incubating medium blocked the spontaneous leak of endogenous 5-HT as well as the release, in the presence of chlorimipramine, evoked either by stimulation of the 5-HT-giant cerebral neurones or high K(+)-media.5. In the presence of chlorimipramine or desmethylimipramine, the duration and/or the amplitude of the excitatory or the inhibitory synaptic potentials evoked in the buccal neurones by the stimulation of the 5-HT giant cerebral neurones were markedly enhanced.6. These results strongly support the idea that 5-HT is the synaptic transmitter released at the excitatory and inhibitory junctions established by the 5-HT giant cerebral neurones in the ipsilateral buccal ganglia. In addition, they underline the role of amine re-uptake in the physiological inactivation of 5-HT as a transmitter.
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PMID:Release of endogenous serotonin from two identified serotonin-containing neurones and the physiological role of serotonin re-uptake. 20 73

Cyclic ADP-ribose (cADPR) is a metabolite of NAD+ that is as active as inositol trisphosphate (IP3) in mobilizing intracellular Ca2+ in sea urchin eggs. The activity of the enzyme responsible for synthesizing cADPR is found not only in sea urchin eggs but also in various mammalian tissue extracts, suggesting that cADPR may be a general messenger for Ca2+ mobilization in cells. An aqueous soluble enzyme, thought to be an NADase, has been purified recently from the ovotestis of Aplysia californica (Hellmich and Strumwasser, 1991). This paper shows that the Aplysia enzyme catalyzes the conversion of NAD+ to cADPR and nicotinamide. The Aplysia enzyme was purified by fractionating the soluble extract of Aplysia ovotestis on a Spectra/gel CM column. The purified enzyme appeared as a single band of approximately 29,000 Da on SDS-PAGE but could be further separated into multiple peaks by high-resolution, cation-exchange chromatography. All of the protein peaks had enzymatic activity, indicating that the enzyme had multiple forms differing by charge. Analysis of the reaction products of the enzyme by anion-exchange high-pressure liquid chromatography (HPLC) indicated no ADP-ribose was produced; instead, each mole of NAD+ was converted to equimolar of cADPR and nicotinamide. The identification of the product as cADPR was further substantiated by proton NMR and also by its Ca(2+)-mobilizing activity. Addition of the product to sea urchin egg homogenates induced Ca2+ release and desensitized the homogenate to authentic cADPR but not to IP3. Microinjection of the product into sea urchin eggs elicited Ca2+ transients as well as the cortical exocytosis reaction. Therefore, by the criteria of HPLC, NMR, and calcium-mobilizing activity, the product was identical to cADPR. To distinguish the Aplysia enzyme from the conventional NADases that produce ADP-ribose, we propose to name it ADP-ribosyl cyclase.
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PMID:ADP-ribosyl cyclase: an enzyme that cyclizes NAD+ into a calcium-mobilizing metabolite. 183 Apr 94

1. Two symmetrical giant neurones located in the cerebral ganglion of Aplysia californica contain 4-6 p-mole 5-hydroxytryptamine (5-HT) and are able to synthesize it (Weinreich, McCaman, McCaman & Vaughn, 1973; Eisenstadt, Goldman, Kandel, Koike, Koester & Schwartz, 1973). Stimulation of each of these neurones evokes excitatory and inhibitory potentials in various cells of the ipsilateral buccal ganglion. In nine buccal neurones it evokes excitatory potentials, in other three, ;classical' inhibitory potentials and in one neurone an ;atypical' inhibitory potential.2. The connexion between the giant cerebral neurone and the cells receiving either an excitatory or a ;classical' inhibitory input from it are monosynaptic. TEA injection into the cerebral giant neurone, which prolongs the presynaptic spike, causes a gradual increase of both the excitatory and the inhibitory potentials. On the other hand, high Ca(2+) media, which block polysynaptic pathways, do not suppress these synaptic potentials.3. The iontophoretic application of 5-HT to the buccal neurones receiving excitatory input from the giant cerebral neurones evokes depolarizations showing the pharmacological properties of both A- and A'-responses to 5-HT (see preceding paper). Antagonists which block only the A-receptors (curare, 7-methyltryptamine, LSD 25) block partially the synaptic depolarizing potentials. Bufotenine, which blocks both the A- and A'-receptors, completely blocks the excitatory potentials. Thus, the post-synaptic membrane of these buccal neurones appears to be endowed with both A- and A'-receptors to 5-HT.4. The ;classical' inhibitory potentials elicited in three buccal neurones are hyperpolarizations which reverse at - 80 mV and are due to an increase in K(+)-conductance. The iontophoretic application of 5-HT to these post-synaptic neurones evokes hyperpolarizing B-responses which are also generated by an increase in K(+)-conductance. Antagonists which block the B-responses (bufotenine, methoxygramine) also block the inhibitory potentials.5. The ;atypical' inhibitory potential evoked in one buccal neurone consists in an hyperpolarization which increases in amplitude with cell hyperpolarization. Iontophoretic application of 5-HT to this buccal cell evokes an hyperpolarizing beta-response which also increases in amplitude with cell polarization and results from a decrease in both Na(+)- and K(+)- conductances. The monosynaptic character of the ;atypical' inhibitory potential is not yet fully proven.6. It can be concluded that the excitatory and inhibitory synaptic effects evoked in the buccal neurones by the stimulation of the 5-HT-containing-giant cerebral neurones are very likely mediated by 5-HT.
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PMID:On the transmitter function of 5-hydroxytryptamine at excitatory and inhibitory monosynaptic junctions. 415 68

In many neurons, variations in membrane excitability are determined by a resting K+ conductance whose magnitude is modulated via neurotransmitters. The S-channel in Aplysia californica mechanosensory neurons is such a conductance, but it has also been shown to be a stretch-activated K+ channel. In this, it resembles stretch-activated K+ channels common to all molluscan neurons. Comparable channels are widespread, having been reported in molluscan and insect muscle and various vertebrate cells. The pore properties of the S-channel and similar stretch-activated K+ channels have received only sporadic attention. Here we examine, at the single-channel level, the permeation characteristics of a stretch-activated K+ channel from neurons of the mollusc Lymnaea stagnalis. Michaelis­Menten constants (Km) for the conductance, obtained separately for inward (28 mmol l-1) and outward (91 mmol l-1) K+ currents, suggest that the channel presents to the external medium, where [K+] is lower, a higher-affinity site than it presents to the cytoplasmic medium. This may help to ensure that influx is not diffusion-limited at potentials near the resting potential, i.e. near the K+ equilibrium constant. Anomalous mole fraction behavior, observed when the ratio of permeant ion (K+ and Rb+) was varied, indicated that the stretch-activated K+ channel is a multi-ion pore. The ion selectivity sequence determined using reversal potentials under bi-ionic conditions was Cs+>K+>Rb+>NH4+>Na+>Li+, and using relative conductance in symmetrical solutions, the sequence was Tl+=K+>Rb+>NH4+>>Na+=Li+=Cs+. Extreme variations in extracellular pH from 4.7 to 11.4 had no effect on stretch-activated K+ channel conductance, whereas normal concentrations of extracellular Mg2+ reduced inward K+ current. Intracellular, but not extracellular, Ba2+ produced a slow, open channel block with an IC50 of 140±80 µmol l-1. These pore properties are compared with those of other stretch-activated K+ channels and of K+ channels in general. In spite of a greater than half order of magnitude difference in the cytoplasmic [K+] in marine (Aplysia californica) and freshwater (Lymnaea stagnalis) molluscs, the conductances of stretch-activated K+ channels from the two groups are very similar.
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PMID:Pore properties of Lymnaea stagnalis neuron stretch-activated K+ channels 931 28

In the nervous system of the marine mollusk Aplysia there are two protein kinase C (PKC) isoforms, the Ca2+-activated PKC Apl I and the Ca2+-independent PKC Apl II. PKC Apl I, but not PKC Apl II is activated by a short-term application of the neurotransmitter serotonin. This may be explained by the fact that purified PKC Apl II requires a higher mole percentage of phosphatidylserine to stimulate enzyme activity than does PKC Apl I. In order to understand the molecular basis for this difference, we have compared the ability of lipids to interact with the purified kinases and with regulatory domain fusion proteins derived from the kinases using a variety of assays including kinase activity, phorbol dibutyrate binding, and liposome binding. We found that a C2 domain fusion protein derived from PKC Apl I binds to lipids constitutively, while a C2 domain fusion protein derived from PKC Apl II does not. In contrast, fusion proteins containing the C1 domains of PKC Apl I and PKC Apl II showed only small differences in lipid interactions. Thus, while the presence of a C2 domain assists lipid-mediated activation of PKC Apl I, it inhibits activation of PKC Apl II.
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PMID:The role of C2 domains in Ca2+-activated and Ca2+-independent protein kinase Cs in aplysia. 966 85