Antagonism by Some Antihistamines of the Amino Acid‐evoked Responses Recorded From the Lobster Muscle Fibre and the Frog Spinal Cord

Abstract

I The effects of some antihistamines on the lobster muscle fibre and the frog spinal cord were investigated using intracellular and extracellular recordings, respectively.2 On lobster muscle, histamine Hl-blockers reversibly antagonized responses to bath-applied glutamate, aspartate and quisqualate but not responses to y-aminobutyric acid (GABA). Iontophoretic glutamate potentials were also reduced. Histamine (up to 1 mM) had no effect on this preparation.3 The Hl-antagonists produced a small increase in muscle membrane conductance and a slight hyperpolarization. These effects were largely unchanged in a low Cl-bathing solution. Procaine (1 mM) decreased membrane conductance and did not affect responses to GABA or glutamate. 4 The H2-antagonist burimamide blocked both glutamate and GABA-evoked responses on the lobster muscle without affecting resting potential or conductance. 5 In the frog cord, bath-applied histamine produced ventral root depolarizations and dorsal root hyperpolarizations (sometimes biphasic responses). These effects were reduced by tetrodotoxin (TTX) but not by antazoline (H,-blocker) or burimamide; the latter reversibly antagonized responses to both glutamate and GABA on TTX-treated cords while antazoline was ineffective. 6 It is suggested that antihistamines can act as non-specific amino acid antagonists by interacting at the level of the receptor-coupled ionophores.

Histamine modulates spinal motoneurons and locomotor circuits

“…Depolarization induced by histamine is likely due, at least in part, to the presence of histaminergic receptors on spinal motoneuron membranes, as suggested by our experiments where synaptic transmission was blocked. This has been previously reported for H 1 and H 2 receptors in the spinal cord (Constanti & Nistri, ; Wu et al, ). Interestingly, the extent of depolarization in the presence of TTX was lower than in physiological solution, indicating that most of the effect is indirect, probably due to recruitment of different neurotransmitters, such as glutamate (Garduño‐Torres, Treviño, Gutiérrez, & Arias‐Montaño, ), acetylcholine (Bacciottini et al, : Munari, Provensi, Passani, & Blandina, ), noradrenaline (Bealer, ), and serotonin (Threlfell et al, ).…”

“…Four metabotropic histamine receptors have been described in the CNS (H 1‐4 ; Haas et al, ), and are also found in spinal tissue (Taylor, Yaksh, & Richelson, [for H 1 subtype]; Murakami, Sun‐Wada, Matsumoto, Wada, & Futai, [for H 2 ]; Cannon et al, [for H 3 ]; Strakhova et al, [for H 4 ]). The effects of H 1 and H 2 receptor activation on spinal motoneurons have been described (Constanti & Nistri, ; Taylor et al, ; Saito et al, ; Wu et al, ).…”

Analysis of histamine as a hair-cell transmitter in the lateral line of Xenopus laevis

“…For example, it is conceivable that the conductance changes associated with NMDA-receptor activation are more susceptible to subtle changes in membrane potential that may have been induced by pyrilamine. In this regard, it is of interest that Constanti and Nistri (1976) reported that pyrilamine altered conductance and produced small changes in the resting membrane potential of lobster muscle fibers. In addition, it is possible that the NMDA receptor-ionophore complex is more susceptible to a non-competitive blockade by pyrilamine.…”

Further Observations on the Interaction Between Gluta Mate and Aspartate on Lobster Muscle

“…Electrotonic potentials were displayed on an oscilloscope and recorded on a chart recorder. In some experiments, a second voltagerecording electrode was introduced at the tendonend of the same fibre in order to calculate the membrane conductance (expressed as gmL, where g. is the conductance per unit length and L the fibre halflength) from 'short' cable theory (see Constanti, 1977 (Takeuchi & Takeuchi, 1964;Constanti & Nistri, 1976c; . However, following a bath-application of glutamate, the subsequent aspartate response was markedly enhanced and then declined progressively to a plateau as before.…”

“…Drugs were dissolved in this solution, adjusted to pH 7.6 and applied via the bathing medium. lontophoretic glutamate and aspartate potentials were obtained by the previously described method (Takeuchi & Takeuchi, 1964;Constanti & Nistri, 1976c; using standard double barrelled microelectrodes. One barrel was filled with 1 M L-Na glutamate (pH 8) and the second with 0.5 to 1 M L-Na aspartate (pH 8) (retaining currents were + 5 to + 30 nA).…”