Non-cyclic AMP-dependent, positive inotropic cyclodepsipeptides with negative chronotropy.

The effects of natural cyclodepsipeptides (CDPs) on isolated rat cardiac tissue preparations were examined in vitro. Destruxin A, destruxin B (DB), roseotoxin B (RB), and roseocardin (RC), a novel CDP, each caused a concentration-dependent increase in the contraction force of the right atrium and the papillary and trabecular muscles of the right ventricle at 0.6 to 600 microM.

Roseocardin, a novel cardiotonic cyclodepsipeptide from Trichothecium roseum TT103.

A new cyclodepsipeptide, designated roseocardin, was isolated from the culture broth of Trichothecium roseum TT103. Roseotoxin B and destruxins A and B were also isolated during the same procedure. The structure of roseocardin was determined by EI-MS, NMR and X-ray crystallographic analysis.

Effects of the mycelial extract of cultured Cordyceps sinensis on in vivo hepatic energy metabolism in the mouse.

Mice were given the extract of cultured Cordyceps sinensis (Cs) (200 mg/kg daily, p.o.) for 3 weeks.

Differential inhibition of transient and long-lasting calcium channel currents by benzodiazepines in neuroblastoma cells.

The effects of diazepam, nitrazepam, clonazepam, and Ro5-4864 on transient (type I) and long-lasting (type II) calcium channels associated with low-affinity benzodiazepine receptors were investigated using the whole-cell patch-clamp technique. Clonazepam (100 microM), a specific agonist for the central-type benzodiazepine receptor, reduced transient currents through the type I calcium channel by 40% without affecting long-lasting currents through the type II calcium channel. Diazepam and nitrazepam (100 microM), non-specific agonists for both the central- and peripheral-type benzodiazepine receptors, reduced both transient and long-lasting currents equally by 25-30%.

Neurally evoked potentiation of tonic contractions in the guinea-pig vas deferens involves adenosine receptors.

1. In the pelvic plexus-vas deferens preparation of the guinea-pig, conditioning stimulation of the pelvic nerves depressed the phasic component of biphasic contractions evoked by test stimulation of the hypogastric nerves, but potentiated the tonic component. 2.

Parasympathetic depression of vas deferens contraction in the guinea-pig involves adenosine receptors.

1. In the guinea-pig pelvic plexus-vas deferens preparation, stimulation of the parasympathetic pelvic nerves contracted the vas deferens then depressed the contractile responses to stimulation of the sympathetic hypogastric nerves. 2.

Gating and permeation properties of two types of calcium channels in neuroblastoma cells.

The gating and permeation properties of two types of calcium channels were studied in the neuroblastoma cell line N1E-115. Calcium channel currents as carried by Ba2+ (50 mM) were recorded using the whole-cell variation of the patch electrode voltage-clamp technique. The two types of calcium channels showed similar membrane potential dependence with respect to the steady-state activation and inactivation gating properties.

Maitotoxin-induced membrane current in neuroblastoma cells.

Maitotoxin (MTX) is a potent marine toxin isolated from the toxic dinoflagellate, Gambierdiscus toxicus. We have examined the possibility of MTX activating calcium channels using cultured neuroblastoma cells (N1E-115). MTX (10 ng/ml) produced a depolarization of the membrane, which was prevented by the removal of Ca2+ from the external medium.

Cyclic nucleotide potentiation of muscarinic responses in neuroblastoma cells.

The role of cyclic nucleotides in modulating acetylcholine-induced and dopamine-induced responses was examined with cultured neuroblastoma N1E-115 cells by means of intracellular recording techniques. Acetylcholine-induced muscarinic hyperpolarization and muscarinic depolarization were potentiated by bath application of a dibutyryl analog of adenosine 3',5'-phosphate (cyclic AMP) or phosphodiesterase inhibitors, 3-isobutyl-1-methylxanthine and 4-(3-butoxy-4-methoxybenzyl)-2-imidazolidinone. Dibutyryl cyclic AMP did not affect the resting membrane potential and membrane resistance.

Characterization of two types of calcium channels in mouse neuroblastoma cells.

1. Two types of voltage-sensitive calcium channels were identified and studied in the neuroblastoma cell line N1E-115. Calcium channel currents as carried by Ba2+ (50 mM) were recorded using the whole-cell variation of the patch-electrode voltage-clamp technique.

Block of calcium channels by enkephalin and somatostatin in neuroblastoma-glioma hybrid NG108-15 cells.

Leucine-enkephalin, methionine-enkephalin, and morphine caused a reversible block of Ca2+ channel currents in neuroblastoma-glioma hybrid cells (NG108-15). The long-lasting (type 2) component of the Ca2+ channel current was blocked by leucine-enkephalin, while the transient (type 1) component was not affected. The enkephalin-induced blocking action was antagonized by naloxone and appears to be mediated by delta-opiate receptors.

Cyclic AMP-mediated potentiation of muscarinic hyperpolarization in neuroblastoma cells.

Adenosine, 2-chloroadenosine and prostaglandin E1 which are known to increase cyclic AMP in neuroblastoma cells potentiated the acetylcholine-induced muscarinic hyperpolarization of the cells without changing the resting membrane potential. The potentiation caused by 2-chloroadenosine was further augmented by Ro 20-1724, a phosphodiesterase inhibitor. A direct intracellular pressure application of cyclic AMP potentiated the muscarinic hyperpolarization without changing the resting membrane potential.

Transplantation of extensor carpi radialis longus muscle in normal and dystrophic chicks.

The etiology of avian muscular dystrophy was examined by a cross-transplantation technique. Care was taken for the transplants to regenerate and develop under neural influence, by using the small extensor carpi radialis longus (ECRL) muscle. The ECRL muscles were exchanged between normal and dystrophic chicks 2 to 3 days ex ovo, and the muscle weight, number of muscle fibers, muscle fiber size, and contractile properties of the transplanted muscles were observed 60 to 65 days after operation when the tissue reconstitution was virtually complete.

Substance P as an excitatory transmitter of primary afferent neurons in guinea-pig sympathetic ganglia.

Electrophysiological and neurochemical experiments were carried out to examine a possible transmitter role substance P in the prevertebral ganglia of the guinea-pig. When potentials were recorded intracellularly from neurons of the isolated ganglia, stimulation of the pre- or postganglionic nerves elicited a non-cholinergic slow excitatory postsynaptic potential (EPSP). This synaptic potential was compared with the effects of substance P.

Role of substance P as a sensory transmitter in spinal cord and sympathetic ganglia.

The hypothesis that substance P (SP) might be a transmitter of primary sensory neurons was first proposed by Lembeck in 1953. A large amount of evidence supporting this hypothesis has recently accumulated, particularly since the elucidation of the chemical structure of SP by Leeman and her colleagues in 1971, which made a number of new approaches possible (e.g.

Enkephalins presynaptically inhibit cholinergic transmission in sympathetic ganglia.

Recent biochemical and immunohistochemical studies have shown that the opioid peptides, enkephalins, occur in nerve terminals and cell bodies in mammalian sympathetic ganglia1-3. Opiates and enkephalins are thought to inhibit synaptic transmission in the peripheral nervous tissues as well as in the central nervous system4-12. The mechanisms of the opiate actions, however, are not entirely clear; both pre- and postsynaptic sites of action have been proposed7-9,11,12.

Substance P: depletion in the dorsal horn of rat spinal cord after section of the peripheral processes of primary sensory neurons.

The substance P content, glutamic acid decarboxylase and choline acetyltransferase activities and the level of [3H]diprenorphine binding were measured in various regions of the lumbar spinal cord of rats after unilateral section of the sciatic nerve or after dorsal rhizotomy. Sciatic nerve section produced a 75--80% depletion of substance P in the dorsal horn but did not change the substance P content of the ventral horn. The onset of substance P depletion occurred within 7 days and was maintained for 2 months.