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Differential effects of centrally‐active antihypertensives on 5‐HT 1A receptors in rat dorso‐lateral septum, rat hippocampus and guinea‐pig hippocampus
Author(s) -
Leishman D.J.,
Boeijinga P.H.,
Galvan M.
Publication year - 1994
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1994.tb14062.x
Subject(s) - guinea pig , hippocampus , agonist , urapidil , hippocampal formation , tetrodotoxin , medicine , 5 ht1a receptor , endocrinology , receptor , chemistry , pharmacology , biology , 5 ht receptor , neuroscience , serotonin , heart rate , blood pressure
1 The electrophysiological responses elicited by 5‐hydroxytryptamine 1A ‐(5‐HT 1A ) receptor agonists in rat and guinea‐pig CA1 pyramidal neurones and rat dorso‐lateral septal neurones were compared in vitro by use of conventional intracellular recording techniques. 2 In the presence of 1 μ m tetrodotoxin (TTX), to prevent indirect effects, 5‐HT, N,N‐dipropyl‐5‐carboxamidotryptamine (DP‐5‐CT) and 8‐hydroxy‐2(di‐n‐propylamino) tetralin (8‐OH‐DPAT) hyperpolarized the neurones from rat and guinea‐pig brain. 3 The hypotensive drug flesinoxan, a selective 5‐HT 1A receptor agonist, hyperpolarized neurones in all three areas tested; however, another hypotensive agent with high affinity at 5‐HT 1A ‐receptors, 5‐methyl‐urapidil, hyperpolarized only the neurones in rat hippocampus and septum. 4 In guinea‐pig hippocampal neurones, 5‐methyl‐urapidil behaved as a 5‐HT 1A ‐receptor antagonist. 5 The relative efficacies (5‐HT = 1) of DP‐5‐CT, 8‐OH‐DPAT, flesinoxan and 5‐methyl‐urapidil at the three sites were: rat hippocampus, 1.09, 0.7, 0.5 and 0.24; rat septum, 0.88, 0.69, 0.82 and 0.7; guinea‐pig hippocampus, 1.0, 0.69, 0.89 and 0, respectively. 6 It is concluded that the hypotensive agents flesinoxan and 5‐methyl‐urapidil appear to have different efficacies at 5‐HT 1A receptors located in different regions of the rodent brain. Whether these regional and species differences arise from receptor plurality or variability in intracellular transduction mechanisms remains to be elucidated.