Actions of picrotoxinin and related compounds on the frog spinal cord: the role of a hydroxyl‐group at the 6‐position in antagonizing the actions of amino acids and presynaptic inhibition

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Abstract
The frog spinal cord has been used to test the effects of naturally occurring picrotoxane compounds (picrotoxinin, picrotin, tutin and coriamyrtin) and semisynthetic ones (6‐acetylpicrotoxinin and anhydropicrotin) on the electrical activities of dorsal and ventral roots and on amino acid‐induced depolarizations of primary afferent terminals. Picrotoxinin, tutin and coriamyrtin (10−5‐3 × 10−5m), which have a free hydroxyl group at the 6‐position, caused a gradual depolarization in both ventral and dorsal roots. The depolarizations were accompanied by a reduction in the size of the dorsal root potential (DR‐DRP), dorsal root reflex (DR‐DRR) and ventral root potential (DR‐VRP) and by an augmentation of the first spike potential and polysynaptic components in the ventral root reflex (DR‐VRR). 6‐Acetylpicrotoxinin (10−5‐3 × 10−5m) caused a slight hyperpolarization in both roots, and this hyperpolarization was accompanied by the augmentation of DR‐DRP, DR‐VRP and DR‐VRR. The DR‐DRR was reduced or abolished by the compound. Picrotoxinin, tutin and coriamyrtin reduced γ‐aminobutyric acid (GABA)‐, β‐alanine‐ and taurine‐induced depolarizations of primary afferent terminals. 6‐Acetylpicrotoxinin showed almost the same degree of inhibition of β‐alanine and taurine as did picrotoxinin, but the GABA‐antagonizing action of the compound was significantly weaker than was that of picrotoxinin. Picrotoxinin, tutin, coriamyrtin and 6‐acetylpicrotoxinin all blocked presynaptic inhibition of the first spike potential caused by antidromic conditioning stimulation. The present results suggest that the hydroxyl group at the 6‐position of picrotoxane compounds are important for antagonism of the effects of GABA, but not of β‐alanine and taurine and for the blocking action of the presynaptic inhibition in the frog spinal cord.