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Vasoactive Intestinal Polypeptide (Vip): A Putative Neurotransmitter In The Cardiovascular System
Published in Geoffrey Burnstock, Susan G. Griffith, Nonadrenergic Innervation of Blood Vessels, 2019
VIP and PHI relax isolated cerebral and peripheral arteries and veins.7, 9, 12, 19, 32-41 Significant motor responses are noted at concentrations of VIP as low as 0.3 nM. The maximum relaxation evoked by PHI or PHM-27 is similar in magnitude to that of VIP (Figure 2). VIP and PHM-27 are equipotent in human temporal arteries (Figure 2A), but PHI is approximately 30 times less potent than VIP in cat cerebral arteries (Figure 2B). In man, there appears to be a more pronounced relaxation of mesenteric veins than of adjacent arteries. The relaxation is not inhibited by the β-adrenoceptor antagonist propranolol, the cholinergic blocker atropine, the histamine H2-antagonists burimamide or metiamide, the cyclo-oxygenase inhibitor indomethacin, or the adenosine blocker theophylline.7, 19, 35 The relaxation is present in arteries from which the endothelium has been removed (Figure 3).37, 39-41 However, a contrary view has been expressed and this may possibly be due to regional or technical differences.42 The vascular response to VIP and PHI is coupled to a concentration-dependent increase in cyclase activity, at least in cerebral vessels (Figure 4) and aorta;37, 41, 43, 44 the cAMP level is increased but the cGMP level appears to be unaltered.37 This action is not shared by secretin or glucagon.43 In the aorta,37 VIP causes a more pronounced increase in cAMP levels than isoprenaline, whereas the isoprenaline-induced relaxation is 86% and the VIP response only 16%. In cerebral vessels VIP causes a 90% relaxation of precontracted arteries but only a 30% increase in the cAMP level.41 Other homologous peptides, human pancreatic growth hormone releasing factor 1-40, secretin, and glucagon, and the VIP fragments, VIP 1-12 and VIP 10-28, are inactive.33
Epilepsy
Published in Divya Vohora, The Third Histamine Receptor, 2008
Divya Vohora, Krishna K. Pillai
The effect of various histaminergic agents on electrically and chemically induced seizures have been summarized in Table 10.1. The i.c.v. administration of histamine and i.p. administration of drugs enhancing brain histamine are generally protective in maximal electroshock (MES) and PTZ-induced convulsions [9,11,12]. A few studies also reported a protective action against picrotoxin (PTX)-induced seizures [8]. However, there were a lot of discrepancies/contradictions among various studies. For instance, histamine administered i.c.v. protected against PTZ-induced seizures in one study [9] but not in the other study [8]. Neither i.c.v. histamine nor i.p. L-histidine could protect mice against PTZ-induced seizures [7]. Furthermore, H3 receptor antagonists were protective against PTZ-induced seizures and kindling in a number of studies [24,35] but were without any effect in a number of other studies [11,25, 26]. A study also reported THP and another H3 antagonist burimamide to increase the severity of PTX-induced clonic convulsions in mice [36]. The dual effects of these compounds could be due to their nonspecificity. For instance, burimamide has also H2 antagonistic activity, whereas THP is an inverse agonist of H3 receptor. In contrast to this study, both THP and clobenpropit were generally found to be effective and were more efficacious against clonic phase of electroconvulsions as compared to the tonic phase [20,23]. This was further supported by the fact that both HDC inhibitors and H1 antagonists exhibited proconvulsant effect in the clonic but not tonic phase [7,12], suggesting that histaminergic drugs may have a potential against generalized absence type of seizures. Furthermore, studies indicate histaminergic agents to be more efficacious against chemoconvulsions in contrast to electroconvulsions. It was suggested that PTZ first stimulates the most sensitive structures in the brain stem and then proceeds to the telencephalon and other brain structures, whereas in case of electroconvulsions, the whole brain is stimulated within 0.2 s, leaving no time for the inhibitory action of histamine [11]. However, Harada et al. [28] reported a reduction of tonic seizures induced by MES following THP, clobenpropit, iodophenpropit, and some other H3 receptor antagonists (VUF5514, VUF5515, and VUF4929) without any effect on the clonic phase, and a potential of these ligands in secondary generalized and tonic-clonic seizures was suggested.
Activation of carbonic anhydrase isoforms involved in modulation of emotional memory and cognitive disorders with histamine agonists, antagonists and derivatives
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2021
Gustavo Provensi, Alessio Nocentini, Maria Beatrice Passani, Patrizio Blandina, Claudiu T. Supuran
Some of these compounds, possessing structures 2–30 (Figure 1), were included in our study for investigating their possible CA activating effects against four pharmacologically relevant human isoforms, hCA I, II, IV and VII. The compounds were numbered according to their similarity to the lead histamine 1 and are: the H1R agonist 2-(2-aminoethyl)thiazole 6; the H2R agonists impromidine 16 and nordimaprit 19; the H3R agonists Nπ-methylhistamine 3, α-methylhistamine 4, methimmepip 8, proxyfan 9, imetit 14, VUF16839 23; the H1R antagonists pyrilamine 24, loratadine 29; the H2R antagonists metiamide 12, cimetidine 13, ranitidine 17, tiotidine 18, zolantidine 20; the H3R antagonists ciproxifan 10, clobenpropit 15, ABT239 22, GSK189254A 28, GSK334429B 30; the H4R antagonists JNJ39758979 25, JNJ7777120 26, A940894 27; the mixed modulators of the histaminergic system Nτ-methylhistamine 2, 4-methylhistamine 5, 1-methylhistidine 7, burimamide 11, betahistine 21.