Pharmacology of amino acid receptors on vertebrate primary afferent nerve fibres.
Structure-activity of primary afferent depolarising action (PAD) mediated by gamma-aminobutyrate (GABA) analogues suggests a difference between subsynaptic receptors located at fibre terminations within the dorsal horn and axonal receptors which are distributed throughout non-synaptic regions. The interaction of the bicuculline-sensitive GABA receptor (GABA A) ionophore complex with barbiturates and benzodiazepines suggests that at least three binding sites are required to explain the independent GABA-mimetic, GABA-potentiating and picrotoxin-reversing effects of such agents. Difficulties with explanation of the depressant effects of baclofen on spinal transmission, in terms of the bicuculline-resistant GABA (GABA B) receptor hypothesis, are mentioned. Glutamate-induced PAD of low threshold afferents is mediated indirectly through release of potassium. However, such terminals possess receptors (possibly autoreceptors for L-glutamate), activated by (+)2-amino-4-phosphonobutyrate, which cause depression of transmitter release. Primary afferent C-fibres possess receptors which are selectively activated by kainate and which mediate picrotoxin-resistant PAD. Such receptors may be involved in the presynaptic conditioning of C-fibre transmitter release. The peripheral terminals of vestibular primary afferents, in amphibia, possess excitatory amino acid receptors which are probably activated by the transmitter released from hair cells.
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D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D001463:Barbiturates / Q000494:pharmacology; D001640:Bicuculline / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D018756:GABA Antagonists; D005971:Glutamates / Q000494:pharmacology; D018698:Glutamic Acid; D006801:Humans; D007608:Kainic Acid / Q000494:pharmacology; D009475:Neurons, Afferent / Q000187:drug effects*; D017459:Receptors, Amino Acid; D011956:Receptors, Cell Surface / Q000187:drug effects*; D011963:Receptors, GABA-A / Q000187:drug effects*; D013329:Structure-Activity Relationship; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D001463:Barbiturates; D018756:GABA Antagonists; D005971:Glutamates; D017459:Receptors, Amino Acid; D011956:Receptors, Cell Surface; D011963:Receptors, GABA-A; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D001418:Baclofen; D007608:Kainic Acid; D001640:Bicuculline