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5-Hydroxytryptamine(1A) receptor activation enhances norepinephrine release from nerves in the rabbit saphenous vein.
J Pharmacol Exp Ther. 1999 Sep; 290(3):1195-201.JP

Abstract

Although serotonergic receptor agonists are known to modulate release of central serotonin, less is known about the ability of serotonin to alter neurotransmission in peripheral adrenergic nerves. The present study used field stimulation (40V, 0.7 ms duration, 1-16 Hz) to contract the rabbit saphenous vein, an effect that was abolished in the presence of tetrodotoxin and prazosin (10(-6) M), consistent with stimulation of neuronal norepinephrine release. Furthermore, the field-stimulated contraction was not altered by the 5-hydroxytryptamine (5-HT)(1B/1D) receptor antagonist GR127935 (10(-6) M), but was markedly inhibited by the 5-HT(1A) receptor antagonist WAY 100635 (10(-6) M). GR127935 (10(-8) M) inhibited contraction to sumatriptan, documenting that the concentration used was sufficient to block 5-HT(1B/1D-like) vascular receptors in this tissue. Likewise, WAY 100635 (10(-6) M) inhibited contraction to the 5-HT(1A) receptor agonists (+/-)-8-hydroxydipropylaminotetralin hydrobromide (8-OH-DPAT) and LY238729, without altering contraction to norepinephrine or sumatriptan. Furthermore, both 8-OH-DPAT and LY228729 enhanced the contractile response to field stimulation (1. 0-8.0 Hz) and activated norepinephrine release in the absence of field stimulation. Contractile responses of the rabbit saphenous vein to both 5-HT(1A) receptor agonists were markedly inhibited by prazosin and dextrally shifted by WAY 100635, supporting the idea that the 5-HT(1A) receptor agonists were activating presynaptic 5-HT(1A) receptors to enhance norepinephrine release even in the absence of field stimulation. Thus, in the rabbit saphenous vein, 5-HT(1A) but not 5-HT(1B/1D) receptors enhanced neurotransmitter release from adrenergic nerves. These observations suggested that serotonergic nerves or other cell types in the saphenous vein are activated by field stimulation to release serotonin, which in turn activates presynaptic 5-HT(1A) receptors on adrenergic neurons to effect norepinephrine release. To support this hypothesis, serotonin levels were measured in the saphenous vein and were increased after pargyline pretreatment (30 mg/kg s.c.), decreased after dl-p-chlorophenylalanine methyl ester pretreatment (300 mg/kg s.c.), and unaltered after pretreatment with 6-hydroxydopamine hydrobromide (100 mg/kg s.c.). Thus, we provide strong evidence for the 1) presence of serotonin and its direct synthesis independent of adrenergic nerves and 2) a novel excitatory effect of presynaptic 5-HT(1A) receptor activation on adrenergic nerves in a peripheral blood vessel.

Authors+Show Affiliations

Lilly Research Laboratories, Lilly Corporate Center, Indianapolis, Indiana, USA. cohenml@lilly.comNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

10454495

Citation

Cohen, M L., et al. "5-Hydroxytryptamine(1A) Receptor Activation Enhances Norepinephrine Release From Nerves in the Rabbit Saphenous Vein." The Journal of Pharmacology and Experimental Therapeutics, vol. 290, no. 3, 1999, pp. 1195-201.
Cohen ML, Schenck KW, Hemrick-Luecke SH. 5-Hydroxytryptamine(1A) receptor activation enhances norepinephrine release from nerves in the rabbit saphenous vein. J Pharmacol Exp Ther. 1999;290(3):1195-201.
Cohen, M. L., Schenck, K. W., & Hemrick-Luecke, S. H. (1999). 5-Hydroxytryptamine(1A) receptor activation enhances norepinephrine release from nerves in the rabbit saphenous vein. The Journal of Pharmacology and Experimental Therapeutics, 290(3), 1195-201.
Cohen ML, Schenck KW, Hemrick-Luecke SH. 5-Hydroxytryptamine(1A) Receptor Activation Enhances Norepinephrine Release From Nerves in the Rabbit Saphenous Vein. J Pharmacol Exp Ther. 1999;290(3):1195-201. PubMed PMID: 10454495.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 5-Hydroxytryptamine(1A) receptor activation enhances norepinephrine release from nerves in the rabbit saphenous vein. AU - Cohen,M L, AU - Schenck,K W, AU - Hemrick-Luecke,S H, PY - 1999/8/24/pubmed PY - 1999/8/24/medline PY - 1999/8/24/entrez SP - 1195 EP - 201 JF - The Journal of pharmacology and experimental therapeutics JO - J Pharmacol Exp Ther VL - 290 IS - 3 N2 - Although serotonergic receptor agonists are known to modulate release of central serotonin, less is known about the ability of serotonin to alter neurotransmission in peripheral adrenergic nerves. The present study used field stimulation (40V, 0.7 ms duration, 1-16 Hz) to contract the rabbit saphenous vein, an effect that was abolished in the presence of tetrodotoxin and prazosin (10(-6) M), consistent with stimulation of neuronal norepinephrine release. Furthermore, the field-stimulated contraction was not altered by the 5-hydroxytryptamine (5-HT)(1B/1D) receptor antagonist GR127935 (10(-6) M), but was markedly inhibited by the 5-HT(1A) receptor antagonist WAY 100635 (10(-6) M). GR127935 (10(-8) M) inhibited contraction to sumatriptan, documenting that the concentration used was sufficient to block 5-HT(1B/1D-like) vascular receptors in this tissue. Likewise, WAY 100635 (10(-6) M) inhibited contraction to the 5-HT(1A) receptor agonists (+/-)-8-hydroxydipropylaminotetralin hydrobromide (8-OH-DPAT) and LY238729, without altering contraction to norepinephrine or sumatriptan. Furthermore, both 8-OH-DPAT and LY228729 enhanced the contractile response to field stimulation (1. 0-8.0 Hz) and activated norepinephrine release in the absence of field stimulation. Contractile responses of the rabbit saphenous vein to both 5-HT(1A) receptor agonists were markedly inhibited by prazosin and dextrally shifted by WAY 100635, supporting the idea that the 5-HT(1A) receptor agonists were activating presynaptic 5-HT(1A) receptors to enhance norepinephrine release even in the absence of field stimulation. Thus, in the rabbit saphenous vein, 5-HT(1A) but not 5-HT(1B/1D) receptors enhanced neurotransmitter release from adrenergic nerves. These observations suggested that serotonergic nerves or other cell types in the saphenous vein are activated by field stimulation to release serotonin, which in turn activates presynaptic 5-HT(1A) receptors on adrenergic neurons to effect norepinephrine release. To support this hypothesis, serotonin levels were measured in the saphenous vein and were increased after pargyline pretreatment (30 mg/kg s.c.), decreased after dl-p-chlorophenylalanine methyl ester pretreatment (300 mg/kg s.c.), and unaltered after pretreatment with 6-hydroxydopamine hydrobromide (100 mg/kg s.c.). Thus, we provide strong evidence for the 1) presence of serotonin and its direct synthesis independent of adrenergic nerves and 2) a novel excitatory effect of presynaptic 5-HT(1A) receptor activation on adrenergic nerves in a peripheral blood vessel. SN - 0022-3565 UR - https://www.unboundmedicine.com/medline/citation/10454495/5_Hydroxytryptamine_1A__receptor_activation_enhances_norepinephrine_release_from_nerves_in_the_rabbit_saphenous_vein_ L2 - https://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=10454495 DB - PRIME DP - Unbound Medicine ER -