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Electrophysiological Studies of 5-Hydroxytryptamine Receptors on Enteric Neurons
Published in T.S. Gaginella, J.J. Galligan, SEROTONIN and GASTROINTESTINAL FUNCTION, 2020
The hyperpolarization caused by 5-HT is associated with a decrease in membrane input resistance and reverses polarity at EK. It was concluded that 5-HT activates a K+ conductance in some neurons to cause a hyperpolarization and inhibition of action potential firing.28,32 Similar data have been obtained using 5-CT and 8-OH-DPAT as agonists. When the hyperpolarization caused by 5-CT is studied in the presence of different extracellular K+ concentrations, the reversal potential for the 5-CT response changed according to the predictions of the Nernst equation for a response mediated by a change in K+ permeability.47 These data led to the conclusion that the 5-HT1A receptor on myenteric AH neurons is coupled to activation of a K+ channel.
Serotonergic and Catecholaminergic Mechanisms for Baroreflex Regulation in the NTS
Published in I. Robin A. Barraco, Nucleus of the Solitary Tract, 2019
To determine whether specific 5-HT agonists can be used to identify serotonergic receptors in vivo, NTS injections of 8-OH-DPAT (a 5-HT1A agonist) and DOI (a 5-HT2A agonist) were tested similarly. 8-OH-DPAT had no appreciable effects, while DOI did not affect blood pressure but reduced heart rate and renal nerve activity slightly. Since these results indicated that 5-HT agonists were unreliable, other experiments were done to test whether specific 5-HT antagonists could be used to alter responses to 5-HT itself. For this purpose, either ketanserin or WB4101 was injected into the NTS as antagonists and responses to 5-HT injected at the same site were recorded. Ketanserin reduced all three responses to 5-HT only partly; specific percent reductions were -34% in mean pressure, -26% in heart rate, and -40% in renal nerve activity. By contrast, WB4101 reduced all responses almost completely, with percent reductions of -95% in mean pressure, -93% in heart rate, and -91% in renal nerve activity. The pronounced inhibition by WB4101 suggests that cardiovascular and sympathetic nerve responses to 5-HT are mediated primarily through 5-HT1A receptors in the NTS. Overall, these results are compatible with the interpretation that 5-HT injected into the NTS acts mainly on 5-HT1A receptors to cause bradycardia through parasympathetic stimulation, and lower blood pressure through sympathetic inhibition.
The Study of Drug Metabolism Using Radiotracers
Published in Graham Lappin, Simon Temple, Radiotracers in Drug Development, 2006
The metabolism of 8-OH DPAT, used experimentally as a serotonin 1A receptor agonist, was studied in the rat.37-3H-8-OH DPAT was administered intraperitoneally, intravenously, or orally to male rats. 8-OH DPAT was tritium labeled in the propyl moiety (Figure 3.24), which, on the face of it, might be considered metabolically unstable, due to possible N-dealkylation (comment was made on this possibility in the paper). Indeed, some N-dealkylation did occur, and this is discussed below. Tritium exchange was assessed by freeze drying and was only around 5%, and therefore could be ignored. The specific activity of the radiolabel was 219 mCi/mmol (8.1 GBq/mmol).
Ginsenoside Re attenuates 8-OH-DPAT-induced serotonergic behaviors in mice via interactive modulation between PKCδ gene and Nrf2
Published in Drug and Chemical Toxicology, 2023
Eun-Joo Shin, Ji Hoon Jeong, Bao-Trong Nguyen, Naveen Sharma, Cuong Ngoc Kim Tran, Seung-Yeol Nah, Yi Lee, Jae Kyung Byun, Sung Kwon Ko, Hyoung-Chun Kim
Consistently, we found that the effect of PKCδ gene knockout on the 8-OH-DPAT-induced overall serotonergic behavior (12 and 30 min after the treatment: p < 0.05 vs. 8-OH-DPAT/WT; 18 and 24 min after the treatment: p < 0.01 vs. 8-OH-DPAT/WT) was more evident in the first 30 min than in the subsequent 30 min, and that the effect of PKCδ gene knockout on the 8-OH-DPAT-induced hypothermia (15 and 75 min after the treatment: p < 0.05 vs. 8-OH-DPAT/WT; 30, 45 and 60 min after the treatment: p < 0.01 vs. 8-OH-DPAT/WT) was the most pronounced 30 min after the administration (Figure 8(G,I)). Thus, we focused on the first 30 min (overall serotonergic behavior) and 30 min (hypothermia) after treatment to examine the effect of GRe on the 8-OH-DPAT-induced overall serotonergic behavior and hypothermia in the present study. As shown in Figure 8(H), GRe, rottlerin, or WAY significantly attenuated (p < 0.01 vs. saline + 8-OH-DPAT) the overall serotonergic behavior induced by 8-OH-DPAT in WT mice. Interestingly, the effect of GRe was comparable with that of rottlerin or WAY, and the effect of PKCδ gene knockout was comparable with that of rottlerin. Consistently, GRe or WAY did not affect the significant attenuation mediated by PKCδ gene knockout in mice. As shown in Figure 8(J), GRe (p < 0.01), rottlerin (p < 0.05), or WAY (p < 0.01) significantly attenuated hypothermia induced by 8-OH-DPAT in WT mice. The effect of GRe was comparable with that of rottlerin or WAY. The effect of PKCδ KO was also comparable with that of rottlerin. Consistently, GRe or WAY treatment did not show any additional effect on the thermoregulation mediated by PKCδ gene knockout in mice.