The effects of capsaicin, citric acid and nicotine applied to the apex or radix of the tongue on taste sensations and salivation were studied in relation to the presence of substance P immunoreactive neurones in man. Application of capsaicin (30 micron) to the apex of the tongue or to the palatinal mucosa, but not to the radix of the tongue, caused a reproducible burning sensation and salivation from the submandibular-sublingual and parotid glands. The salivation response to capsaicin was reduced by methylscopolamine pretreatment. Similar levels of substance P immunoreactivity were present in the lingual apex and radix area (including vallate papillae) of man, while in the cat about 4 times higher levels of substance P immunoreactivity were present in the vallate papillae than in the lingual apex. Immunohistochemistry showed that in the cat many substance P immunoreactive nerves were associated with the taste buds of the vallate papillae, while in man substance P immunoreactive fibres were only seen penetrating into the epithelium of the lingual apex. In addition some subepithelial blood vessels in all regions were surrounded by substance P immunoreactive nerves in both cat and man. Citric acid application to the tongue apex caused both submandibular-sublingual and parotid salivary secretion concomitant with a burning sensation. Salivary secretion was also seen after citric acid application to the radix of the tongue. This response was associated with a sour taste. The salivation response to citric acid was not significantly reduced by methylscopolamine pretreatment. Lingual apex application of nicotine was associated with a sweet taste and a small rise in salivary secretion rate. This response was not significantly reduced by methylscopolamine. In conclusion, the sensitivity to capsaicin of the human tongue is restricted to the apex portion. This is in parallel with the occurrence of intraepithelial substance P immunoreactive nerve fibres. Capsaicin induced salivary secretion seems mainly to be mediated via parasympathetic, cholinergic reflex mechanisms. Citric acid and nicotine induced salivation responses are comparatively more resistant to methylscopolamine pretreatment.
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