Role of beta-adrenergic receptor subtypes in pig uterus contractility with inflammation

Sikora

et al. 2022

Sci Rep

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This study analyzed severe acute endometritis action on myometrial density and distribution of protein gene product (PGP)9.5- and calcitonin gene-related peptide (CGRP)-like immunoreactive nerve fibers and calcitonin receptor-like receptor (CLR) expression, and on CGRP receptor (CGRPR) participation in uterine contractility in pigs. E. coli suspension (E. coli group) or saline (SAL group) were injected into the uteri, or only laparotomy was performed (CON group). In the E. coli group myometrium, a lack of significant changes in PGP9.5 and CGRP innervation patterns and increased CLR protein level were revealed. In all groups, compared to the pretreatment period, human αCGRP increased amplitude in the myometrium, while reducing it in endometrium/myometrium. In the E. coli group endometrium/myometrium, human αCGRP lowered amplitude vs other groups. Human αCGRP reduced frequency in CON and SAL groups and enhanced it in the E. coli group endometrium/myometrium. The frequency in E. coli group increased vs other groups. CGRPR antagonist, human αCGRP8–37, reversed (CON, SAL groups) and eliminated (E. coli group) the rise in human αCGRP-induced myometrial amplitude. In endometrium/myometrium, human αCGRP8–37 abolished (CON group) and reversed (SAL group) a decrease in frequency, and reduced the rise in frequency (E. coli group) caused by human αCGRP. Collectively, in the myometrium, endometritis did not change PGP9.5 and CGRP innervation patterns and enhanced CLR protein level. CGRPR also mediated in CGRP action on inflamed uterus contractility.

Section: Discussionmentioning

confidence: 92%

mentioning

confidence: 97%

Involvement of the calcitonin gene-related peptide system in the modulation of inflamed uterus contractile function in pigs

Sikora

et al. 2022

Sci Rep

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“…In inflamed pig uterus, presence of all α1-and α2-ARs isoforms and all β-ARs subtypes [13], and the lowering effect of NA on its contractility were also revealed [24]. Moreover, the role of particular β-ARs subtypes [16] and particular α2-ARs isoforms [25] in the contractility of pig uterus with inflammation was documented. No data are available on the role of particular α1-ARs isoforms in the contractility of inflamed uterus.…”

Section: Introductionmentioning

confidence: 85%

“…Under physiological conditions, expression of all isoforms of α1-and α2-ARs, and all subtypes of β-ARs, was revealed in myocytes of myometrium (MYO) in animals [5][6][7][8][9][10][11][12][13]. Activation of α-ARs by NA stimulates, while activation of β-ARs decreases, myometrial contractility [14][15][16]. All isoforms of α1-ARs participate in the regulation of rat uterine contractility [5,6,8,17].…”

Section: Introductionmentioning

confidence: 99%

Effect of blocking of alpha1-adrenoreceptor isoforms on the noradrenaline-induced changes in contractility of inflamed pig uterus

2023

PLoS ONE

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Background Disturbances in uterine contractility often lead to the origin, development and maintenance of endometritis and metritis, which are a very common and serious pathologies in domestic animals. Here we aimed to investigate the role of α1A-, α1B- and α1D-adrenoreceptors (ARs) in noradrenaline (NA)-induced contractility of inflammatory-changed porcine uterus. Methods On Day 3 of the estrous cycle, either Escherichia coli (E. coli) suspension (E. coli group) or saline (SAL group) was injected into uterine horns, or only laparotomy was performed (CON group). Eight days later, infected gilts developed severe acute endometritis. Results Compared to the period before NA application, NA reduced the contractile amplitude and frequency in myometrium (MYO) and endometrium (ENDO)/MYO strips from the CON, SAL and E. coli groups. In the last group, the amplitude in MYO and the frequency in ENDO/MYO were lowered versus other groups. After using α1A-ARs antagonist with NA, a greater decrease or occurrence of a drop in the amplitude and frequency in all groups (ENDO/MYO) were found compared to this neurotransmitter action alone. Such results were noted for NA action on the frequency after α1B-ARs blocking in the CON (both kinds of strips) and SAL (ENDO/MYO) groups. In response to α1D-ARs antagonist with NA, a greater decrease or occurrence of a drop in the amplitude was noted in the CON (both kinds of strips) and SAL and E. coli (MYO) groups. Use of these factors caused the similar changes in the frequency in CON and E. coli (MYO) and SAL (ENDO/MYO) groups. In response to NA, α1A,B,D-ARs antagonist led to a greater reduction or appearance of a drop in the amplitude in the CON and SAL (ENDO/MYO) and E. coli (both kinds of strips) as well as in the frequency in the CON and SAL (ENDO/MYO) and E. coli (MYO) groups. Conclusions In conclusion, activation of α1A- and α1D-ARs by NA promotes the contractile amplitude and frequency in the inflamed pig uterus; pharmacological modulation of these receptors can be utilized to enhance systolic activity of myometrium.

“…With regard to the control of inflamed uterus contractility, the importance of metabolites of arachidonic acids, such as prostaglandin (PG)F2α [ 8 ], PGE2 [ 9 ], PGI2 [ 10 ], leukotriene (LT)C4 and LTD4 [ 11 ] in pigs, as well as PGF2α during the postpartum period in cows [ 12 ], have been reported. Studies have also been devoted to the role of noradrenaline (NA) [ 9 , 10 , 13 , 14 , 15 ], acetylcholine (ACh) [ 16 , 17 ], neuropeptide Y (NPY) [ 18 ], somatostatin [ 19 ], vasoactive intestinal peptide (VIP) [ 20 ] and galanin (GAL) [ 21 ] in the contractility of porcine inflamed uterus, together with the function of receptors for these neurotransmitters.…”

Section: Introductionmentioning

confidence: 99%

Investigation of the Role of Pituitary Adenylate Cyclase-Activating Peptide (PACAP) and Its Type 1 (PAC1) Receptor in Uterine Contractility during Endometritis in Pigs

Witek

2022

IJMS

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Uterine inflammation is a common pathology in animals, leading to disturbances in reproductive processes and reduced production profitability. Pituitary adenylate cyclase-activating peptide (PACAP) effects at the uterine level during inflammation are not known. In the current study, we analyzed the relative PACAP type 1 receptor (PAC1R) mRNA transcript and protein abundances in the myometrium (MYO), as well s PACAP and PAC1R involvement in the contractile function of inflamed pig uterus. To that end, E. coli suspension (E. coli group) or saline (SAL group) was injected into the uterine horns or laparotomy was performed (CON group). Eight days after the bacteria injections, severe acute endometritis and a reduced relative abundance of PAC1R protein in the MYO were observed. Compared to the period before PACAP in vitro administration, PACAP (10−7 M) in the CON and SAL groups decreased in amplitude in the MYO and endometrium (ENDO)/MYO, whereas in the E. coli group, increased amplitude in the MYO and reduced amplitude in the ENDO/MYO were observed. In the E. coli group, PACAP enhanced the amplitude in the MYO (10−7 M) and decreased the amplitude in the ENDO/MYO (10−8 M) compared with other groups. PACAP (10−7 M) increased the frequency of both kinds of strips in the CON and SAL groups compared with the pretreatment period. PACAP (both doses) did not significantly change the frequency in the E. coli group, whereas in response to PACAP (10−7 M), the frequency was reduced compared to other groups. In the MYO, PAC1R antagonist decreased the amplitude reduction (CON and SAL groups) and reversed a rise in PACAP (10−7 M)-evoked amplitude (E. coli group). PAC1R blocking reversed (MYO) and abolished (ENDO/MYO) the stimulatory effect of PACAP (10−7 M) on the frequency (CON and SAL groups). PAC1R antagonist and PACAP (10−7 M) evoked the appearance of frequency depression in both kinds of strips (E. coli group). In summary, in pigs, severe acute endometritis reduces the relative abundance of PAC1R protein in the MYO, and PAC1R mediates the influence of PACAP on inflamed uterus contractility.