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Characterization of sensory neurotransmission and its inhibition via α2B-adrenoceptors and via non-α2-receptors in rabbit iris

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Summary

To find out whether, and which type of, adrenoceptors mediate prejunctional inhibition of sensory neurotransmitter release from trigeminal fibres, the modulation of twitch response to electrical field stimulation on rabbit isolated iris was investigated. Evoked iris sphincter contractions consisted of a minor fast cholinergic and a large slow component. The latter was unaffected by atropine and guanethidine, hence nonadrenergic noncholinergic in nature (NANC), but nearly completely abolished by capsaicin pretreatment and by the neurokinin receptor antagonist spantide. The response was probably not mediated by NK2 receptors as SR 48,968, an NK2 selective nonpeptide antagonist, failed to reduce the response to the release of the endogenous neurokinin(s) (and exogenous substance P), but in part due to NK1 receptor activation as shown by a reduction of response by CP 96,345, an NK1 selective non-peptide antagonist, and in part perhaps mediated by NK3 receptors. A small neurokinin receptor antagonist- and capsaicin-insensitive NANC contraction is probably not mediated by CGRP receptors.

The α2-adrenoceptor agonist oxymetazoline inhibited the evoked NANC response (22 nmol/1, IC20; about 40%, maximum inhibition) without affecting the cholinergic response (up to 1 μmol/1) or the postjunctional iris sensitivity to exogenous substance P. The inhibition was antagonized by rauwolscine (apparent -log KB 8.04) and by the relatively α2B-adrenoceptor selective antagonist ARC-239 (-log KB 8.51).

The α2- and imidazoline receptor agonist aganodine inhibited the evoked NANC response (0.25 μmol/l, IC20; about 30%, maximum inhibition) without affecting the postjunctional substance P responses. Rauwolscine 0.3 μmol/l failed to antagonize this effect.

It is concluded that the release of sensory neurotransmitter(s) from trigeminal fibres in the rabbit eye may be inhibited by α2B-adrenoceptors and by a non-α2-receptor, perhaps an imidazoline receptor.

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  1. Pharmakologisches Institut der Universität Mainz, Obere Zahlbacher Strasse 67, W-6500, Mainz, Federal Republic of Germany

    Hermann Fuder & Michael Selbach

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  1. Hermann Fuder
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  2. Michael Selbach
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This study was supported by the Deutsche Forschungsgemeinschaft (Fu 163/3)

Correspondence to H. Fuder at the above address

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Fuder, H., Selbach, M. Characterization of sensory neurotransmission and its inhibition via α2B-adrenoceptors and via non-α2-receptors in rabbit iris. Naunyn-Schmiedeberg's Arch Pharmacol 347, 394–401 (1993). https://doi.org/10.1007/BF00165389

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  • DOI: https://doi.org/10.1007/BF00165389

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