5-HT inhibits spontaneous contractility of isolated sheep mesenteric lymphatics via activation of 5-HT(4) receptors.
Spontaneous isometric contractions were measured in rings of sheep mesenteric lymphatic vessels in vitro. 5-Hydroxytryptamine (5-HT) produced a concentration-dependent decrease in spontaneous contraction frequency and force which was not antagonised by either the nonspecific 5-HT(1)/5-HT(2) receptor antagonist methysergide (1 microM) or the 5-HT(3) receptor antagonist ondansetron (1 microM). The 5-HT(4) receptor agonist BIMU-8 mimicked the inhibitory effect of 5-HT and its effects were abolished by the 5-HT(4) receptor antagonist DAU 6285 (1 microM). DAU-6285 also abolished the inhibitory effect of 5-HT and unmasked a weak excitatory response, which was mimicked by the 5-HT(2) receptor agonist alpha-methyl-5-hydroxytryptamine maleate. This excitatory response was, in turn, blocked by the 5-HT(2) receptor antagonist pirenperone (1 microM). The results of this study suggest that sheep mesenteric lymphatics possess both 5-HT(4) receptors and 5-HT(2) receptors. The inhibitory 5-HT(4) receptor appeared to be the predominant subtype since the excitatory response to 5-HT could only be observed in the presence of the 5-HT(4) receptor antagonist DAU 6285.
McHale
N G
NG
Smooth Muscle Group, Department of Physiology, Queen's University, 97 Lisburn Road, Belfast, BT9 7BL, Northern Ireland.
Thornbury
K D
KD
Hollywood
M A
MA
D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology; D066298:In Vitro Techniques; D007537:Isometric Contraction / Q000187:drug effects; D008208:Lymphatic System / Q000187:drug effects* / Q000502:physiology; D008784:Methysergide / Q000494:pharmacology; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D017294:Ondansetron / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000502:physiology; D044422:Receptors, Serotonin, 5-HT4; D012701:Serotonin / Q000031:analogs & derivatives / Q000494:pharmacology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D012756:Sheep
D001562:Benzimidazoles; D019086:Bridged Bicyclo Compounds, Heterocyclic; D010880:Piperidines; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; C074390:DAU 6285; C070189:(endo-N-8-methyl-8-azabicyclo-(3.2.1)oct-3-yl)-2,3-dihydro-3-isopropyl-2-oxo-1H-benzimidazol-1-carboxamide; D044422:Receptors, Serotonin, 5-HT4; C042390:alpha-methylserotonin; D012701:Serotonin; D017294:Ondansetron; D008784:Methysergide; C034177:pirenperone