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Pharmacological Characterization of 5-Hydroxytryptamine Receptors in the Gastrointestinal Tract
Published in T.S. Gaginella, J.J. Galligan, SEROTONIN and GASTROINTESTINAL FUNCTION, 2020
Jeremy D. Gale, Keith T. Bunce
This group of receptors, all of which are negatively coupled to adenylyl cyclase, has the greatest number of identified subtypes to date. However, only two members of this family, 5-HT1A and 5-HT1D, have so far been identified in the GI tract.5,6 The 5-HT1P receptor, not classically a member of this group, will be included in the later section concerning orphan 5-HT receptors. All the receptor subtypes included in this group have a number of common properties. Firstly, they exhibit high affinity for 5-HT. Secondly, 5-carboxamidotryptamine (5-CT) is a full agonist with greater potency than that of 5-HT (equieffective concentration ratio compared to 5-HT = 0.04–0.4).7 Finally, the receptors are sensitive to blockade by a number of antagonists including methiothepin (metitepine). However, this compound is neither selective for a particular subtype of 5-HT receptor (5-HT1A: pKB = 7.7;8 5-HT1D: pA2 = 7.8;9 5-HT2: pKD = 8.6),10 nor specific for 5-HT receptors (α1-adrenoceptor: pKi = 9.411; α2-adrenoceptor: pA2= 6.2;12 histamine H1: pKi = 8.311). Moreover, practical experience reveals that methiothepin is a difficult compound to use in vitro as it adheres to plastic and, to a lesser extent, glass. Methysergide also demonstrates binding affinity for both 5-HT1A (pKi = 7.6)13 and 5-HT1D receptors (pKD = 7.6–8.4).14 However, the functional activity of methysergide at 5-HT1D receptors may in fact be that of an agonist,15 and in many systems, methysergide also appears to be a partial agonist at 5-HT1A receptors.16,17 Furthermore, like methiothepin, methysergide is an antagonist at 5-HT2 receptors (pA2 = 8.5),18 although it possesses little adrenoceptor antagonist activity.11
Pindolol potentiates the antidepressant effect of venlafaxine by inhibiting 5-HT1A receptor in DRN neurons of mice
Published in International Journal of Neuroscience, 2021
Corradeti et al. (1998) reported that pindolol blocks the inhibition induced by ipsapiron, 5-HT1A receptor agonist, in the neurons of rat DRN with extracellular electrophysiological recording [26]. They have also shown that the hyperpolarizing effect of 5-CT (5-carboxamidotryptamine), a non-selective 5-HT receptor agonist, on the DRN neurons was blocked by pindolol in the same study [26]. Consistently, in the current study, pindolol blocked the inhibition of the DRN neurons induced by 5-HT and 8-OHDPAT in the DRN. We, for the first time, demonstrated that pindolol blocked all the 5-HT1A-mediated current that was induced by 8-OHDPAT in voltage clamp conditions. This appear to imply that pindolol with a partial agonistic effect on the 5-HT1A receptors [18] can prevent this inhibition when used in combination with antidepressants increasing the level of 5-HT in the somatodendritic region.
The 5-HT7 receptor antagonist SB-269970 alleviates seizure activity and downregulates hippocampal c-Fos expression in pentylenetetrazole-induced kindled rats
Published in Neurological Research, 2022
Bilal Sahin, Ercan Ozdemir, Erkan Gumus, Mustafa Ergul, Ahmet Sevki Taskiran
Before experimental application Pentylenetetrazole (PTZ), 5-Carboxamidotryptamine (5-CT, 5-HT7 agonist) and SB-269970 (5-HT7 antagonist) dissolved in saline. All agents were administered intraperitoneally. All research drugs were purchased from Sigma-Aldrich (Co. St Louis, MO).