piperidines and tryptoline

Neural networks that regulate an organism's internal environment must sense perturbations, respond appropriately, and then reset. These adaptations should be reflected as changes in the efficacy of the synapses that drive the final output of these homeostatic networks. Here we show that hemorrhage, an in vivo challenge to fluid homeostasis, induces LTD at glutamate synapses onto hypothalamic magnocellular neurosecretory cells (MNCs). LTD requires the activation of postsynaptic alpha2-adrenoceptors and the production of endocannabinoids that act in a retrograde fashion to inhibit glutamate release. In addition, both hemorrhage and noradrenaline downregulate presynaptic group III mGluRs. This loss of mGluR function allows high-frequency activity to potentiate these synapses from their depressed state. These findings demonstrate that noradrenaline controls a form of metaplasticity that may underlie the resetting of homeostatic networks following a successful response to an acute physiological challenge.

Topics: Adrenergic alpha-Agonists; Adrenergic alpha-Antagonists; Animals; Animals, Newborn; Biophysics; Carbolines; Clonidine; Down-Regulation; Drug Interactions; Egtazic Acid; Electric Stimulation; Excitatory Amino Acid Agents; Excitatory Postsynaptic Potentials; Glutamic Acid; Guanosine Diphosphate; Hypothalamus; In Vitro Techniques; Intracranial Hemorrhages; Long-Term Synaptic Depression; Male; Microinjections; Neurons; Patch-Clamp Techniques; Piperidines; Pyrazoles; Rats; Rats, Sprague-Dawley; Receptor, Cannabinoid, CB1; Receptors, Metabotropic Glutamate; Synapses; Thionucleotides; Yohimbine

An enzymatic preparation from human brain converts tryptamine to tryptoline (9H-1,2,3,4-tetrahydropyrido[3,4-b]indole) in the presence of 5-methyltetrahydrofolic acid. Similarly, N-methyltryptamine and 5-hydroxytryptamine yield 1-methyltryptoline and 5-hydroxytryptoline, respectively. Neither in vitro nor in vivo formation of these compounds by human tissues has been described.

Topics: Brain; Carbolines; Humans; Hydrogen-Ion Concentration; Indoles; Kinetics; Methylation; Piperidines; Structure-Activity Relationship; Tetrahydrofolates; Tissue Extracts; Tryptamines

Topics: Adult; Amines; Blood Platelets; Carbolines; Chromatography; Crystallization; Female; Humans; In Vitro Techniques; Indoles; Male; Mass Spectrometry; Methylation; Middle Aged; Piperidines; Serotonin; Sex Factors; Tetrahydrofolates; Tryptamines