Adrenergic stimulation-released 5-HT stored in adrenergic nerves inhibits CGRPergic nerve-mediated vasodilatation in rat mesenteric resistance arteries

Hirohito Fujii, Shingo Takatori, Yoshito Zamami, Narumi Hashikawa-Hobara, Natsuki Miyake, Panot Tangsucharit, Mitsunobu Mio, Hiromu Kawasaki

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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 ÂμM) 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.

Original languageEnglish
Pages (from-to)2084-2094
Number of pages11
JournalBritish Journal of Pharmacology
Volume166
Issue number7
DOIs
Publication statusPublished - Aug 2012

Fingerprint

Mesenteric Arteries
Vasodilation
Adrenergic Agents
Serotonin
Vasoconstriction
Methysergide
Desipramine
Receptor, Serotonin, 5-HT1D
Perfusion
Serotonin 5-HT1 Receptor Antagonists
Guanethidine
Adrenergic Neurons
Serotonin Antagonists
Adrenergic Antagonists
Calcitonin Gene-Related Peptide
Fluoxetine
Serotonin Receptors
Endothelium
Catecholamines
Blood Vessels

Keywords

  • 5-HT
  • adrenergic nerve
  • calcitonin gene-related peptide-containing nerves
  • perivascular nerve interaction
  • rat mesenteric artery

ASJC Scopus subject areas

  • Pharmacology

Cite this

Adrenergic stimulation-released 5-HT stored in adrenergic nerves inhibits CGRPergic nerve-mediated vasodilatation in rat mesenteric resistance arteries. / Fujii, Hirohito; Takatori, Shingo; Zamami, Yoshito; Hashikawa-Hobara, Narumi; Miyake, Natsuki; Tangsucharit, Panot; Mio, Mitsunobu; Kawasaki, Hiromu.

In: British Journal of Pharmacology, Vol. 166, No. 7, 08.2012, p. 2084-2094.

Research output: Contribution to journalArticle

Fujii, Hirohito ; Takatori, Shingo ; Zamami, Yoshito ; Hashikawa-Hobara, Narumi ; Miyake, Natsuki ; Tangsucharit, Panot ; Mio, Mitsunobu ; Kawasaki, Hiromu. / Adrenergic stimulation-released 5-HT stored in adrenergic nerves inhibits CGRPergic nerve-mediated vasodilatation in rat mesenteric resistance arteries. In: British Journal of Pharmacology. 2012 ; Vol. 166, No. 7. pp. 2084-2094.
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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 {\^A}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.",
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AU - Hashikawa-Hobara, Narumi

AU - Miyake, Natsuki

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AU - Mio, Mitsunobu

AU - Kawasaki, Hiromu

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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 ÂμM) 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.

AB - 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 ÂμM) 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.

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KW - rat mesenteric artery

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