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Adrenergic stimulation-released 5-HT stored in adrenergic nerves inhibits CGRPergic nerve-mediated vasodilatation in rat mesenteric resistance arteries.
Br J Pharmacol. 2012 Aug; 166(7):2084-94.BJ

Abstract

BACKGROUND AND PURPOSE

5-HT is taken up by and stored in adrenergic nerves and periarterial nerve stimulation (PNS) releases 5-HT to cause vasoconstriction in rat mesenteric arteries. The present study investigated whether PNS-released 5-HT stored in adrenergic nerves affects the function of perivascular calcitonin gene-related peptide-containing (CGRPergic) nerves.

EXPERIMENTAL APPROACH

Rat mesenteric vascular beds without endothelium and with active tone were perfused with Krebs solution. Changes in perfusion pressure in response to PNS and CGRP injection were measured before (control) and after perfusion of Krebs solution containing 5-HT (10 µM) for 20 min. Distributions of 5-HT- and TH-immunopositive fibres in mesenteric arteries were studied using immunohistochemical methods.

KEY RESULTS

PNS (1-4 Hz) frequency dependently caused adrenergic nerve-mediated vasoconstriction followed by CGRPergic nerve-mediated vasodilatation. 5-HT treatment inhibited PNS-induced vasodilatation without affecting exogenous CGRP-induced vasodilatation, while it augmented PNS-induced vasoconstriction. Guanethidine (adrenergic neuron blocker), methysergide (non-selective 5-HT receptor antagonist) and BRL15572 (selective 5-HT1D receptor antagonist) abolished inhibition of PNS-induced vasodilatation in 5-HT-treated preparations. Combined treatment with 5-HT and desipramine (catecholamine transporter inhibitor), but not fluoxetine (selective 5-HT reuptake inhibitor), did not inhibit PNS-induced vasodilatation. Exogenous 5-HT inhibited PNS-induced vasodilatation, which was antagonized by methysergide. In immunohistochemical experiments, 5-HT-immunopositive nerves, colocalized with adrenergic TH-immunopositive nerves, were observed only in 5-HT-treated mesenteric arteries, but not in control preparations or arteries co-treated with desipramine.

CONCLUSIONS AND IMPLICATIONS

These results suggest that 5-HT can be taken up by and released from adrenergic nerves in vitro by PNS to inhibit CGRPergic nerve transmission in rat mesenteric arteries.

Authors+Show Affiliations

Department of Clinical Pharmaceutical Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

22394392

Citation

Fujii, Hirohito, et al. "Adrenergic Stimulation-released 5-HT Stored in Adrenergic Nerves Inhibits CGRPergic Nerve-mediated Vasodilatation in Rat Mesenteric Resistance Arteries." British Journal of Pharmacology, vol. 166, no. 7, 2012, pp. 2084-94.
Fujii H, Takatori S, Zamami Y, et al. Adrenergic stimulation-released 5-HT stored in adrenergic nerves inhibits CGRPergic nerve-mediated vasodilatation in rat mesenteric resistance arteries. Br J Pharmacol. 2012;166(7):2084-94.
Fujii, H., Takatori, S., Zamami, Y., Hashikawa-Hobara, N., Miyake, N., Tangsucharit, P., Mio, M., & Kawasaki, H. (2012). Adrenergic stimulation-released 5-HT stored in adrenergic nerves inhibits CGRPergic nerve-mediated vasodilatation in rat mesenteric resistance arteries. British Journal of Pharmacology, 166(7), 2084-94. https://doi.org/10.1111/j.1476-5381.2012.01935.x
Fujii H, et al. Adrenergic Stimulation-released 5-HT Stored in Adrenergic Nerves Inhibits CGRPergic Nerve-mediated Vasodilatation in Rat Mesenteric Resistance Arteries. Br J Pharmacol. 2012;166(7):2084-94. PubMed PMID: 22394392.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Adrenergic stimulation-released 5-HT stored in adrenergic nerves inhibits CGRPergic nerve-mediated vasodilatation in rat mesenteric resistance arteries. AU - Fujii,Hirohito, AU - Takatori,Shingo, AU - Zamami,Yoshito, AU - Hashikawa-Hobara,Narumi, AU - Miyake,Natsuki, AU - Tangsucharit,Panot, AU - Mio,Mitsunobu, AU - Kawasaki,Hiromu, PY - 2012/3/8/entrez PY - 2012/3/8/pubmed PY - 2012/12/10/medline SP - 2084 EP - 94 JF - British journal of pharmacology JO - Br J Pharmacol VL - 166 IS - 7 N2 - BACKGROUND AND PURPOSE: 5-HT is taken up by and stored in adrenergic nerves and periarterial nerve stimulation (PNS) releases 5-HT to cause vasoconstriction in rat mesenteric arteries. The present study investigated whether PNS-released 5-HT stored in adrenergic nerves affects the function of perivascular calcitonin gene-related peptide-containing (CGRPergic) nerves. EXPERIMENTAL APPROACH: Rat mesenteric vascular beds without endothelium and with active tone were perfused with Krebs solution. Changes in perfusion pressure in response to PNS and CGRP injection were measured before (control) and after perfusion of Krebs solution containing 5-HT (10 µM) for 20 min. Distributions of 5-HT- and TH-immunopositive fibres in mesenteric arteries were studied using immunohistochemical methods. KEY RESULTS: PNS (1-4 Hz) frequency dependently caused adrenergic nerve-mediated vasoconstriction followed by CGRPergic nerve-mediated vasodilatation. 5-HT treatment inhibited PNS-induced vasodilatation without affecting exogenous CGRP-induced vasodilatation, while it augmented PNS-induced vasoconstriction. Guanethidine (adrenergic neuron blocker), methysergide (non-selective 5-HT receptor antagonist) and BRL15572 (selective 5-HT1D receptor antagonist) abolished inhibition of PNS-induced vasodilatation in 5-HT-treated preparations. Combined treatment with 5-HT and desipramine (catecholamine transporter inhibitor), but not fluoxetine (selective 5-HT reuptake inhibitor), did not inhibit PNS-induced vasodilatation. Exogenous 5-HT inhibited PNS-induced vasodilatation, which was antagonized by methysergide. In immunohistochemical experiments, 5-HT-immunopositive nerves, colocalized with adrenergic TH-immunopositive nerves, were observed only in 5-HT-treated mesenteric arteries, but not in control preparations or arteries co-treated with desipramine. CONCLUSIONS AND IMPLICATIONS: These results suggest that 5-HT can be taken up by and released from adrenergic nerves in vitro by PNS to inhibit CGRPergic nerve transmission in rat mesenteric arteries. SN - 1476-5381 UR - https://www.unboundmedicine.com/medline/citation/22394392/Adrenergic_stimulation_released_5_HT_stored_in_adrenergic_nerves_inhibits_CGRPergic_nerve_mediated_vasodilatation_in_rat_mesenteric_resistance_arteries_ L2 - https://doi.org/10.1111/j.1476-5381.2012.01935.x DB - PRIME DP - Unbound Medicine ER -