The aim of the current study was to identify enteric 5-HT(4) splice variants, locate enteric 5-HT(4) receptors, determine the relationship, if any, of the 5-HT(4) receptor to 5-HT(1P) activity, and to ascertain the function of 5-HT(4) receptors in enteric neurophysiology. 5-HT(4a), 5-HT(4b), 5-HT(4e), and 5-HT(4f) isoforms were found in mouse brain and gut. The ratio of 5-HT(4) expression to that of the neural marker, synaptophysin, was higher in gut than in brain but was similar in small and large intestines. Submucosal 5-HT(4) expression was higher than myenteric. Although transcripts encoding 5-HT(4a) and 5-HT(4b) isoforms were more abundant, those encoding 5-HT(4e) and 5-HT(4f) were myenteric plexus specific. In situ hybridization revealed the presence of transcripts encoding 5-HT(4) receptors in subsets of enteric neurons, interstitial cells of Cajal, and smooth muscle cells. IgY antibodies to mouse 5-HT(4) receptors were raised, affinity purified, and characterized. Nerve fibers in the circular muscle and the neuropil in ganglia of both plexuses were highly 5-HT(4) immunoreactive, although only a small subset of neurons contained 5-HT(4) immunoreactivity. No 5-HT(4)-immunoreactive nerves were detected in the mucosa. 5-HT and 5-HT(1P) agonists evoked a G protein-mediated long-lasting inward current that was neither mimicked by 5-HT(4) agonists nor blocked by 5-HT(4) antagonists. In contrast, the 5-HT(4) agonists renzapride and tegaserod increased the amplitudes of nicotinic evoked excitatory postsynaptic currents. Enteric neuronal 5-HT(4) receptors thus are presynaptic and probably exert their prokinetic effects by strengthening excitatory neurotransmission.

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The effect of CO2 laser irradiation on pulpal microcirculation was studied in cat canines. The enamel surfaces of 4 teeth were exposed with energy densities of 304-1440J/cm2, using either a handpiece or a microslad, with a focal spot of 0.21mm and 0.33mm respectively. Pulpal blood flow (PBF) before and following lasing was recorded through the intact tooth surface by a laser Doppler flowmeter. CO2 laser irradiation caused an increase in PBF, which was immediate and transient. The PBF increase was higher in a large pulp than in a small pulp, and it was inversely related to the focal spot size. These findings confirm that the dental pulp is thermally affected by CO2 lasing of the tooth surface, however, without extensive pulp coagulation. It is concluded that the effects of laser irradiation on the pulpal microcirculation may be studied in situ by means of the presented methodology.

Potassium ion-containing solutions have been shown to initially excite then depress intradental nerve activity (INA) when applied into deep dentinal cavities. The INA reflects activity originating in intradental A fibers. Application of KCl to deep dentinal cavities also induces an increase in pulpal blood flow (PBF). Capsaicin is known to exert a highly selective desensitizing effect on polymodal C-fiber nerve endings. These C fibers are generally believed to release vasoactive substances in response to stimulation. In order to determine if KCl exerts its vascular effect via activation of capsaicin-sensitive nerve fibers, we examined blood flow and sensory nerve responses to KCl obtained before and after capsaicin desensitization. The A-fiber nerve activity was determined by using INA recording technique. Blood flow was measured simultaneously from the same tooth using laser Doppler flowmetry. Local application of 0.25 M KCl to a deep dentinal cavity induced a brief spike burst and an increase in PBF of 76.0 +/- 14.6% (n = 8). Repeated applications of 0.25 M KCl caused a consistent increase in the peak PBF amplitude (n = 8). Local application of 100 microM capsaicin to a deep dentinal cavity caused an increase in PBF of 116.8 +/- 26.3% (n = 8) lasting 12-18 min, but capsaicin application did not appear to evoke any INA response. The amplitude of PBF in response to capsaicin application declined during repeated applications. Following repeated applications of capsaicin the PBF response to KCl was significantly reduced (9.9 +/- 4.3%, n = 8).(ABSTRACT TRUNCATED AT 250 WORDS)

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