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Nature of 5HT1like receptors mediating depressor responses in vagosympathectomized rats; close resemblance to the cloned 5ht7 receptor

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Abstract

It has been suggested that the late hypotensive response to serotonin (5hydroxytryptamine; 5HT) in vagosympathectomized rats is mediated by ‘5HT1like’ receptors since this effect is mimicked by 5carboxamidotryptamine (5CT), is not modified by cyproheptadine, ketanserin or MDL72222, but it is blocked by methysergide. The present study was set out to reanalyze this suggestion in terms of the classification schemes proposed in 1994 and 1996 by the NCIUPHAR subcommittee on the classification and nomenclature of 5HT receptors. I.v. bolus injections of 5CT (0.010.3μg·kg1), 5HT (130μg·kg1) and 5methoxytryptamine (5MeOT; 130μg·kg1) produced dosedependent hypotensive responses with a rank order of agonist potency: 5CT >> 5HT ≥ 5methoxytryptamine with sumatriptan (301000μg·kg1) inactive. The depressor responses to 5HT and 5CT were not attenuated by i.v. GR127935 (3003000μg·kg1) or equivalent volumes of saline. In contrast, lisuride, methiothepin, mesulergine, metergoline and clozapine dose-dependently antagonized the responses to 5HT and 5CT; the rank order of apparent pA2 values against 5HT and 5CT, respectively, was: lisuride (7.7; 7.8) > methiothepin (6.8; 7.0) ≥ mesulergine (6.4; 6.6) > clozapine (5.7; 5.8); metergoline displayed variable potencies (5.6; 6.4). Except for lisuride, which also affected isoprenalineinduced hypotension, the antagonism by the other drugs was selective. Based upon the above rank order of agonist potency, the blockade by a series of drugs showing high affinity for the cloned 5ht7 receptor and the lack of blockade by GR127935, our results indicate that the 5HT receptor mediating hypotension in vagosympathectomized rats is operationally similar to other putative 5ht7 receptors mediating vascular and nonvascular responses (e.g. relaxation of the rabbit femoral vein, canine coronary and external carotid arteries and guineapig ileum as well as feline tachycardia).

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Received: 11 February 1997 / Accepted: 1 April 1997

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Vries, P., Villalón, C., Heiligers, J. et al. Nature of 5HT1like receptors mediating depressor responses in vagosympathectomized rats; close resemblance to the cloned 5ht7 receptor. Naunyn-Schmiedeberg's Arch Pharmacol 356, 90–99 (1997). https://doi.org/10.1007/PL00005034

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  • DOI: https://doi.org/10.1007/PL00005034

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