Hiroyuki Akagi

A potent metabotropic glutamate receptor agonist: electrophysiological actions of a conformationally restricted glutamate analogue in the rat spinal cord and Xenopus oocytes

The (2S,3S,4S) isomer of alpha-(carboxycyclopropyl)glycine (L-CCG-I), a conformationally restricted glutamate analogue, caused a marked depolarization of motoneurons in the isolated rat spinal cord, which was almost insensitive to CPP and CNQX. Depolarizing responses to L-CCG-I were markedly decreased by reducing the temperature of the bathing fluid. Similar results were obtained in the case of trans-ACPD, which is a metabotropic glutamate receptor agonist, but the depolarizing action of L-CCG-I was more potent than that of trans-ACPD. In Xenopus oocytes injected with poly(A)+ mRNA extracted from the rat brain, L-CCG-I induced significant oscillatory chloride currents, suggesting that L-CCG-I is a potent agonist for metabotropic-type glutamate receptors.

Identification of two taurine receptor subtypes on the primary afferent terminal of frog spinal cord

1 Effects of taurine on primary afferent terminals in the frog spinal cord were examined by a sucrose‐gap method applied to a dorsal root (9th or 10th segment). 2 In a normal Ringer solution, taurine (1 mM, applied for 5 s at a rate of 0.04 ml s−1, 0.2 μmol) caused a hyperpolarization, but a higher concentration (10 mM, applied at the same rate, 2.0 μmol) caused a biphasic response consisting of a hyperpolarization followed by a slow onset depolarization. A similar biphasic response could also be observed in tetrodotoxin‐treated preparations. 3 When the concentration of extracellular Mg2+ was increased up to 9.0 mM, the depolarizing response to taurine was augmented. The rate of the augmentation was dependent upon the extracellular Mg2+ concentration. 4 The depolarizing effect was selectively antagonized by bicuculline in concentrations (10–30 μm) that had no significant antagonizing action on γ‐aminobutyric acid (GABA)‐induced depolarization. On the other hand the hyperpolarizing effect of taurine was selectively reduced by strychnine (0.1 μm) which had no antagonizing effect on responses to glycine. 5 These results suggest that in the frog spinal cord there are at least two subtypes of taurine receptor whose pharmacological profiles resemble GABA and glycine receptors in the mammalian central nervous system, and whose sensitivity may be modulated by extracellular Mg2+.

GABAergic modulation of a substance P‐mediated reflex of slow time course in the isolated rat spinal cord

1 The effects of γ‐aminobutyric acid (GABA) and other drugs which interact with GABA receptors were studied on a reflex of slow time course in the spinal cord preparation isolated from the neonatal rat. 2 A single shock to a dorsal root (L3‐L5) elicited a stereotyped series of reflexes, consisting of fast and slow components, recorded from the contralateral ventral root of the corresponding segment. The slow component, i.e. the contralateral slow ventral root potential (v.r.p.) had a time‐to‐peak of 2–5 s and lasted 20–30 s. 3 Bath‐application of GABA (5–20 μm) or muscimol (0.05‐0.5 μm) caused a decrease in the amplitude of the contralateral slow v.r.p. without producing any change in the d.c. potential recorded from the ventral root. The monosynaptic reflex recorded from the ipsilateral ventral root was not changed by the drugs at these concentrations. 4 Diazepam (0.1−1 μm) potentiated the depolarizing response of the dorsal root to GABA and markedly depressed the contralateral slow v.r.p. Neither the d.c. potential of the ventral root nor the dorsal root was changed by diazepam. The monosynaptic reflex was also unaffected by the drug. 5 Bicuculline (1 μm) suppressed the GABA‐induced depolarization recorded from the dorsal root whilst it markedly potentiated the contralateral slow v.r.p. 6 Baclofen at concentrations from 0.01 to 0.1 μm reduced the contralateral slow v.r.p. The inhibitory action of baclofen on the contralateral slow v.r.p. was more marked than on the monosynaptic reflex. 7 The depolarization of the ventral root induced by a brief application of substance P (SP) was depressed by muscimol, diazepam and baclofen, whereas the depolarization was potentiated by bicuculline. 8 The present results suggest that an intraspinal GABAergic inhibitory mechanism plays a role in the modulation of certain slow spinal reflexes. They also support the hypothesis that SP released from certain primary afferent fibres is a neurotransmitter involved in the contralateral slow v.r.p.

Opposite actions of forskolin at pre- and postsynaptic sites in rat sympathetic ganglia

In isolated rat superior cervical ganglia, forskolin, a powerful activator of adenylate cyclase, augmented the amplitude of fast excitatory postsynaptic potentials. Quantal analysis showed that forskolin acts presynaptically to facilitate the release of the transmitter. The time course of the presynaptic action of forskolin paralleled that of the increase in cyclic AMP level in the ganglia. In addition, forskolin exerted a postsynaptic action on the nicotinic acetylcholine receptor so that the acetylcholine-induced depolarization was depressed. The action of forskolin on the nicotinic acetylcholine receptor seems to be unrelated to the cyclic AMP system.