Receptors mediating the effects of 5‐hydroxytryptamine on the tracheal vasculature and smooth muscle of sheep

Webber, Stephanie; Salonen, Raimo O.; Widdicombe, J. G.

doi:10.1111/j.1476-5381.1990.tb14647.x

Cited by 11 publications

(12 citation statements)

References 26 publications

(25 reference statements)

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“…Unfortunately the vasoconstrictor action was inconsistent and possibly masked by the vasodilatation and could not be studied further. This dual action of a single mediator on the sheep tracheal circulation has also been seen for histamine and 5-HT (Webber et al, 1990) although the mechanisms are not always clear. The vasoconstrictions seen here could be produced by the release of 5-HT from platelets by PAF.…”

Section: Discussionmentioning

confidence: 91%

Mechanisms of platelet activating factor‐induced changes in sheep tracheal blood flow

Corfield

Webber

Widdicombe

1991

British J Pharmacology

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1 The effects of platelet activating factor (PAF) have been studied on the cervical tracheal vasculature and smooth muscle of anaesthetized sheep. 2 The predominant action of PAF (2 pmol-2 nmol) was a dose-dependent fall in tracheal vascular resistance. The maximum fall in resistance was -41.6% (-38.5 to -44.7%, 95% confidence interval) and the ED50 was 17 pmol (12-28 pmol). Lyso-PAF (200 pmol) did not change vascular resistance.3 PAF had no effect on tracheal smooth muscle tone assessed by measuring changes in the external diameter of the trachea. 4 The fall in vascular resistance produced with PAF was unaffected by the anti-asthma drug nedocromil sodium (1 mg, i.a.), the cyclo-oxygenase inhibitor indomethacin (5mg kg-, i.v.), the leukotriene receptor antagonist FPL55712 (2mgkg-1, i.v.), or a combination of the histamine H1-and H2-antagonists mepyramine (2 mg kg-1, i.v.) with cimetidine (5 mg kg-1, i.v.). The PAF antagonist WEB 2086 (300,ug kg-1, i.v.) significantly reduced the vasodilatation produced by PAF (before, -40.8 + 4.2%; after -16.5 + 5.9%, P <0.05). 5 Thus in this model, PAF is a potent vasodilator of the tracheal circulation but has no action on tracheal smooth muscle. The vasodilatation is mediated by specific PAF receptors and is not due to the release of prostanoids, leukotrienes or histamine.

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Section: Discussionmentioning

confidence: 91%

Mechanisms of platelet activating factor‐induced changes in sheep tracheal blood flow

Corfield

Webber

Widdicombe

1991

British J Pharmacology

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“…Previously, Webber et al [31] demonstrated the existence of a biphasic 5-HT-mediated re- sponse in the tracheal vasculature of sheep although they reported a contraction followed by relaxation. In our study, however, the transient relaxation only occurred in 30% of all the tissues analysed.…”

Section: Discussionmentioning

confidence: 99%

Serotonin Induces a Biphasic Response in Rabbit Cavernosal Smooth Muscle: Relevance to the Erectile Process

et al. 2007

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Introduction: Serotonin (5-hydroxytryptamine; 5-HT) can cause contraction in cavernosal smooth muscle. We further evaluated this effect of 5-HT. Methods: Organ bath studies were used. Results: 5-HT induced a sustained contraction occasionally accompanied by a transient relaxation (in 30% of rabbit cavernosal tissues) that preceded the contraction. Ondansetron and Y-25130 (both 5-HT₃ receptor antagonists) but not SB-269970 (a 5-HT₇ receptor antagonist) significantly inhibited or abolished this transient relaxation. Doxazosin (dox, an α₁-receptor antagonist) and ketanserin (ketan, a 5-HT_2A receptor antagonist) significantly inhibited or abolished the sustained contraction. The effects of dox on 5-HT-mediated contraction were concentration-dependent. Conclusions: Our findings further confirm that the peripheral serotonergic pathway may play a part in the erectile process via 5-HT_2A receptor-mediated contractile and 5-HT₃ receptor-mediated relaxant activities. Our results also support the findings of human studies, which suggest that both ketan and dox may exert beneficial effects on the erectile process.

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“…In fact, 2-methyl-5-HT has no significant effect on tracheal smoothmuscle tone (120). The failure of atropine and morphine to influence 5-HT-induced responses of the airway smooth muscle of cats makes it unlikely that 5-HT acts indirectly by a release of ACh through stimulation of 5-HT3 neuronal receptors.…”

Section: -Htmentioning

confidence: 96%

“…Moreover, it has been shown that 5-HT contracts tracheal smooth muscle in the sheep by stimulation of 5-HT 1-like receptors and constricts the tracheal vascular bed by stimulation of 5-HT2 receptors or dilates the vascular bed by stimulation of 5-HTi-like receptors (120). In general, activation of the 5-HTilike class of receptors produces the presynaptic inhibitory effects of 5-HT on neurons (43) and relaxation of smooth muscle (45), although it can also produce contraction of smooth muscle (64).…”

Section: -Htmentioning

confidence: 99%

Effects of serotonin on airways: recent developments

Cazzola

D’Amato

et al. 1995

Allergy

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Serotonin (5-hydroxytryptamine, 5-HT) is an endogenous autacoid that can modulate activity in visceral sensory nerves. It produces complex physiologic actions within the cardiopulmonary system by interacting with both vascular and airway smooth-muscle 5-HT receptors (51). Although the role of 5-HT in humoral control of airway tone is not known, several interactions between this monoamine and the lung have been described. 5-HT is actively transported by the pulmonary endothelial cells where it is metabolized by monoamine oxidase, perhaps accounting for an affinity site on the outer layer of the mitochondria (112). Radio autographic localization has confirmed that pulmonary endothelial cells are the site of 5-HT uptake (112). Effects of 5-HT on airways5-HT is believed to have direct, complex indirect, or both actions on smooth muscle and nervous structures (51). The airway responses to 5-HT appear to be a summation of ongoing excitatory and inhibitory signals triggered or modified by this monoamine. A contractile response has been reported in airway muscle preparations from guinea pig, cat, dog, horse, cow, sheep, and calf (1,12,30,44,83,89, 108,117). No response is observed in the trachea and bronchus of rat, rabbit, and pig (27, 29), whereas a relaxation caused by 5-HT can be observed in goat trachea (28). Both in vivo and in vitro airway responses to 5-HT are often not as intense as to histamine or cholinergic agonists, may show tachyphylaxis, and may be partially or completely inhibited by pretreatment with atropine (62).5-HT causes constriction of both central and peripheral airways when given to vagotomized cats (34). However, the net effect of 5-HT infusion depends on the dose infused. Small amounts can induce air expulsion, while larger doses induce air retention because ofthe constriction ofthe large airways. Bronchoconstriction of large airways as well as of peripheral airways was observed in dogs during 5-HT perfusion by mechanical studies (38).The significance of 5-HT as a bronchoconstrictor in man remains to be determined. Experiments with tracheal muscle strips and bronchial spirals have shown that 5-HT causes weak contractions (10% of maximum) (37), although it can cause both constriction and relaxation of bronchioles and bronchi, depending on the concentration used (25,77,82). 5-HT causes relaxation when tone is induced in isolated human bronchial muscle preparations, an effect not blocked by 5-HT antagonists. In contrast, pulmonary vascular preparations always contract in 1

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Receptors mediating the effects of 5‐hydroxytryptamine on the tracheal vasculature and smooth muscle of sheep

Cited by 11 publications

References 26 publications

Mechanisms of platelet activating factor‐induced changes in sheep tracheal blood flow

Mechanisms of platelet activating factor‐induced changes in sheep tracheal blood flow

Serotonin Induces a Biphasic Response in Rabbit Cavernosal Smooth Muscle: Relevance to the Erectile Process

Effects of serotonin on airways: recent developments

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