5-Hydroxytryptamine increases contractile force in porcine right atrium but not in left ventricle

Schoemaker, Regien G.; Du, Xiao Y.; Bax, Willem A.; Saxena, Pramod R.

doi:10.1007/bf00169001

Cited by 29 publications

(19 citation statements)

References 9 publications

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“…Peripherally, 5-HT4 receptors affect motility of the gastrointestinal tract and mediate increases in the porcine and human atria1 rate and contractility (Table 5). Interestingly, 5-HT4 receptors seem to be absent on porcine Schoemaker et al, 1992), as well as human (Jahnel et al, 1992;Schoemaker et al, 1993) ventricles.…”

Section: Responses Mediated By Serotonin Receptorsmentioning

confidence: 96%

Serotonin receptors: Subtypes, functional responses and therapeutic relevance

Saxena

1995

Pharmacology & Therapeutics

195

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Abstract-Recent, rapid progress in the molecular biology of serotonin (5HT) receptors requires conceptual re-thinking with respect to receptor classification. Thus, based on operational criteria (agonist and antagonist rank order), as well as transduction mechanisms involved and the structure of the receptor protein, the Nomenclature Committee of the Serotonin Club has proposed the following classification and nomenclature: the main receptor types 5-HT, to S-HT4, recombinant receptors (e.g. 5-ht, to 5-ht7) and 'orphan' receptors. The aim of the present review is to discuss the events leading to this classification, the criteria for and functional responses mediated by various 5-HT receptors, as well as the therapeutic possibilities with 5-HT ligands.

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Section: Responses Mediated By Serotonin Receptorsmentioning

confidence: 96%

Serotonin receptors: Subtypes, functional responses and therapeutic relevance

Saxena

1995

Pharmacology & Therapeutics

195

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“…The pig is one of the few species to possess atrial 5-HT 4 receptors, and porcine atrium is considered a good model for human atrial 5-HT 4 receptors ; Medhurst and Kaumann 1993;Schoemaker et al 1992). Activation of Gprotein-coupled 5-HT 4 receptors starts a complex signalling cascade involving cAMP-mediated activation of protein kinase A (PKA) that ultimately leads to positive inotropic and lusitropic responses in left and right atrium Sanders and Kaumann 1992).…”

Section: Introductionmentioning

confidence: 99%

Study of the regulation of the inotropic response to 5-HT4 receptor activation via phosphodiesterases and its cross-talk with C-type natriuretic peptide in porcine left atrium

Weninger¹,

Maeyer

Lefebvre³

2012

Naunyn-Schmiedeberg's Arch Pharmacol

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We studied how 5-HT(4) receptor-mediated inotropic responses are regulated at the level of cAMP in porcine left atrium. We used selective phosphodiesterase (PDE) inhibitors to assess which PDE subtypes are responsible for the fade with time of inotropic responses to 5-HT(4) receptor activation with 5-HT and the 5-HT(4) receptor agonist prucalopride. A possible cross-talk via PDEs between cGMP and 5-HT(4) receptor-induced cAMP signalling was evaluated. Electrically paced left atrial pectinate muscles from young male pigs (15-25 kg) were studied in vitro. Simultaneous inhibition of PDE3 plus PDE4 subtypes was necessary to increase the amplitude and completely prevent the fade of the inotropic response to 5-HT and prucalopride. When responses to 5-HT or prucalopride had faded 1 h after addition, the nonspecific PDE-inhibitor IBMX still fully recovered inotropic responses. Stimulation of particulate guanylyl cyclase, together with PDE2 and PDE4 inhibition, delayed the fade of the response to 5-HT, while stimulation of soluble guanylyl cyclase independently of PDEs accelerated the fade of the response to 5-HT. In conclusion, both PDE3 and PDE4 subtypes are responsible for the suppression and the fade of the inotropic response to 5-HT and prucalopride. Signalling through the 5-HT(4) receptor remains fully active for at least 90 min with PDEs continuously regulating the response. cGMP levels, elevated by activation of particulate guanylyl cyclase under PDE2 inhibition, can indirectly enhance 5-HT(4) receptor-mediated signalling, at least when also PDE4 is inhibited, presumably through inhibition of PDE3. Elevation of cGMP generated by soluble guanylyl cyclase attenuates responses to 5-HT independently of PDEs.

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“…In contrast, the inotropic effect was not observed in porcine [9] and human ventricles [13]. The effects were more complex in the canine heart [16], where direct negative inotropic and indirect positive inotropic effects were seen.…”

Section: Introductionmentioning

confidence: 87%

“…The inotropic effect of 5-HT has been reported to be direct in cat atria [5,6], guinea pig atria [5,7], rat hearts [8], porcine atriä [9], and human atria [10][11][12][13]; whereas indirect effects were reported for rabbit hearts [5,14,15]. In contrast, the inotropic effect was not observed in porcine [9] and human ventricles [13].…”

Section: Introductionmentioning

confidence: 99%

Diverse inotropic effects of 5-hydroxytryptamine in heart muscles of various mammalian species

et al. 1996

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The inotropic effects of 5-hydroxytryptamine (5-HT) on mammalian heart muscles were investigated. 5-HT (10(-8)-10(-3)M) produced increases in the contractile tension of atrial and ventricular muscles isolated from guinea pigs, Japanese monkeys, and humans, but not in rat heart preparations. The maximum percent increase of contraction was largest in guinea pig ventricular muscles (142.0 percent), followed by monkey atrium (86.3 percent), human atrium (71.7 percent), guinea pig atrium (48.7 percent), and monkey ventricle (30.1 percent). The sensitivity to 5-HT, measured as the negative logarithm of the half-maximal inotropic molar contractions of 5-HT, i.e., -logEC(50), was highest in the human atrium (6.65 +/- 0.20), followed by guinea pig atrium (5.53 +/- 0.36), monkey ventricle (4.83 +/- 0.28), guinea pig ventricle (4.56 +/- 0.11), and monkey atrium (4.46 +/- 0.16). The inotropic effects of 5-HT seen in the atrial and ventricular muscles of guinea pigs were abolished in the presence of the beta-receptor blocker, pindolol (8 mu M), while these effects in human atrial muscles and monkey atrial and ventricular muscles were abolished only in the presence of both pindolol (8 mu M) and of prazosin (1 mu M), an alpha(1)-receptor blocker. 5-HT increased the V(max) of the slow response recorded from guinea pig ventricular muscles exposed to high K+ (27 mM) media, whereas this agent did not alter the calcium current of isolated guinea pig ventricular myocytes devoid of sympathetic nerve terminals. In reserpinized guinea pig hearts, 5-HT exerted no inotropic effect on ventricular muscle, yet it had an inotropic effect in the atrial muscle, although the latter effect was considerably depressed, compared to that seen in non-reserpinized atrial muscles. We conclude that the positive inotropic effects of 5-HT observed in the ventricular muscle of the guinea pig and in the atrial and ventricular muscles of the Japanese monkey can be attributed to the release of noradrenaline from sympathetic nerve terminals (indirect effect). In contrast, in human atrial muscles, the positive inotropic effect of 5-HT was apparently the result of stimulation of a specific membrane receptor for 5-HT (direct effect). In guinea pig atrial muscles, both direct and indirect effects of 5-HT were involved in the positive inotropism. An explanation for the lack of sensitivity of rat atrial and ventricular muscles to 5-HT awaits further studies.

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5-Hydroxytryptamine increases contractile force in porcine right atrium but not in left ventricle

Cited by 29 publications

References 9 publications

Serotonin receptors: Subtypes, functional responses and therapeutic relevance

Serotonin receptors: Subtypes, functional responses and therapeutic relevance

Study of the regulation of the inotropic response to 5-HT4 receptor activation via phosphodiesterases and its cross-talk with C-type natriuretic peptide in porcine left atrium

Diverse inotropic effects of 5-hydroxytryptamine in heart muscles of various mammalian species

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