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Title: Ruolo funzionale dei recettori β-adrenergici nella motilità del miometrio di suino
Other Titles: Functional role of β-adrenoceptors in the motility of pig myometrium
Authors: Ganapini, Matteo
Issue Date: 15-Oct-2020
Publisher: Università di Parma. Dipartimento di Scienze Medico-Veterinarie
Document Type: Master thesis
Abstract: The aim of the present project was to evaluate the feasibility of studies on porcine uterus preparations in vitro, in order to characterize the functional role of β-adrenergic receptors on spontaneous uterine motility of non-pregnant pigs. The preparations of longitudinal smooth muscle of uterine horn showed a certain degree of spontaneous motility, likely supported by action potentials activated by pacemaker-like cells. The characterization of this spontaneous motility was performed with the help of specific substances that allowed us to better understand the mechanisms underlying the contractions. Indeed, the phasic contractile activity was not modified neither by tetrodotoxin, nor by local anaesthetic drugs, excluding both the involvement of activation mechanisms of neuronal origin and the involvement of voltage-gated sodium channels. Moreover, atropine was also ineffective, showing that these contractions are not induced by activation of muscarinic receptors. In contrast, nitric oxide synthase inhibitor, L-NAME, produced an increase in the amplitude of the contraction, suggesting an active role of nitric oxide as a modulator of this motility. In addition, Ca2+ ions seem to play an important role in supporting spontaneous contractile activity of pig myometrium. In fact, the preparations were sensitive to the inhibitory effects of different Ca2+ channel blockers, such as nifedipine, verapamil and diltiazem, while compound BAY K 8644, an activator of L-type Ca2+ channels, enhanced both amplitude and frequency of contractions, and antagonised, in an apparently competitive-surmountable way, the inhibitory effect by nifedipine. Isoproterenol (non-selective β-adrenergic agonist), fenoterol, salbutamol and ritodrine (selective β2-adrenergic agonists) reduced the amplitude of contractions of the longitudinal smooth muscle of the uterine horn in a concentration-dependent manner, causing an almost complete abolition of spontaneous motility at concentrations of 10-7/10-6 M. The order of efficacy based on the Emax values obtained was: isoproterenol (100%) > ritodrine (97.8 ± 1.7%) > fenoterol (93, 2 ± 6.8%) > salbutamol (86.1 ± 12.2%) > clenbuterol (23.9 ± 15.0%). The order of potency based on the calculated pEC50 values was: fenoterol (8.90 ± 0.24) ≥ ritodrine (8.72 ± 0.13) > salbutamol (7.99 ± 0.54) ≥ isoproterenol (7.84 ± 0.18) > clenbuterol (7.52 ± 0.86). 7 The results obtained from our study suggest that β-adrenergic receptors are involved in the relaxation of spontaneous contractions of the myometrium of the non-pregnant uterus in pigs. Propranolol and bupranolol, non-selective β-adrenergic antagonists, at a concentration of 10-7 M, antagonized the inhibitory effect on contraction caused by isoproterenol, fenoterol and ritodrine. These effects seem to confirm that the relaxation of the contractions of the porcine uterus induced by β-agonist drugs is indeed due to the activation of adrenergic receptors of the β type. Furthermore, since the simultaneous blockade of β1, β2 and β3 receptors by bupranolol was not more effective in antagonizing the effects of the agonists with respect to β1-β2 block by propranolol, it can be hypothesized that, in our experimental conditions, β3 receptors do not play a major role in the inhibitory control of these contractions. The use of selective antagonists for single β-adrenergic receptor subtypes allowed us to better characterize the β-adrenergic receptor population present in the porcine myometrium in our experimental conditions. ICI 118.551, a highly selective β2 receptor antagonist, induced a negligible shift in the concentration-effect curve of ritodrine. Conversely, bisoprolol, a selective β1-adrenergic receptor antagonist, induced a moderate shift in the concentration-effect curve of isoproterenol. These data suggest a marginal role by β2-adrenergic receptors, whereas β1-adrenergic receptors seem instead to play an important role in agonist-induced smooth muscle relaxation of swine myometrium. These results are particularly interesting, since, unlike what has been shown in other species, including humans, they seem to indicate that β-adrenergic relaxation of spontaneous contractions of the non-pregnant pig myometrium is mainly mediated β1-adrenergic receptors, while the contribution of β2 and β3 receptors is of lower relevance. Further experiments with highly selective agonist and antagonist of different β-adrenergic receptor subtypes will be necessary to better characterize the receptor subpopulations involved in the regulation of spontaneous contractions of porcine myometrium.
Appears in Collections:Scienze medico-veterinarie

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