Regulatory Influence of Galanin and GALR1/GALR2 Receptors on Inflamed Uterus Contractility in Pigs

Abstract

Uterine inflammation is a very common and serious pathology in domestic animals, the development and progression of which often result from disturbed myometrial contractility. We investigated the effect of inflammation on the protein expression of galanin (GAL) receptor subtypes (GALR)1 and GALR2 in myometrium and their role in the contractile amplitude and frequency of an inflamed gilt uterus. The gilts of the E. coli and SAL groups received E. coli suspension or saline in their uteri, respectively, and only laparotomy was performed (CON group). Eight days later, the E. coli group developed severe acute endometritis and lowered GALR1 protein expression in the myometrium. Compared to the pretreatment period, GAL (10−7 M) reduced the amplitude and frequency in myometrium and endometrium/myometrium of the CON and SAL groups, the amplitude in both stripes and frequency in endometrium/myometrium of the E. coli group. In this group, myometrial frequency after using GAL increased, and it was higher than in other groups. GALR2 antagonist diminished the decrease in amplitude in myometrium and the frequency in endometrium/myometrium (SAL, E. coli groups) induced by GAL (10−7 M). GALR1/GALR2 antagonist and GAL (10−7 M) reversed the decrease in amplitude and diminished the decrease in frequency in both examined stripes (CON, SAL groups), and diminished the drop in amplitude and abolished the rise in the frequency in the myometrium (E. coli group). In summary, the inflammation reduced GALR1 protein expression in pig myometrium, and GALR1 and GALR2 participated in the contractile regulation of an inflamed uterus.

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

“…In addition to the substances listed above, the drop in the amplitude in the porcine uterus with endometritis is caused by NPY, VIP and GAL [ 18 , 20 , 21 ], whereas PGF2α, PGI2, LTC4 and LTD4 increased the value of this parameter [ 8 , 9 , 11 ]. In the present report, the authors extended those findings by demonstrating that PACAP increases the myometrial amplitude, which may lead to the removal of inflammatory exudate from the uterine lumen.…”

“…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.…”

Uterine Inflammation Changes the Expression of Cholinergic Neurotransmitters and Decreases the Population of AChE-Positive, Uterus-Innervating Neurons in the Paracervical Ganglion of Sexually Mature Gilts

“…Alternatively, GAL may modulate the activity of other neurotransmitter systems, which, in turn, influence cholinergic transmission. Moreover, GAL has been proven to stimulate uterine contractility [64,65] and change the amplitude and frequency of uterine contractions [66]. Thus far, cholinergic, GAL-expressing neurons have been shown to exist in brain formations such as the basal forebrain and the hippocampus [67].…”

Effects of Substance P and Neurokinin A on the Contractile Activity of Inflamed Porcine Uterus

“…This is particularly important due to the fact that disturbances in uterine contractile activity contribute to the development of inflammation and its subsequent consequences [ 31 ]. Our previous studies have shown that the contractile amplitude and frequency in pigs are partly different between the myometrium and the endometrium/myometrium in response to active substances, e.g., galanin, ACh, somatostatin, neuropeptide Y and PGs [ 7 , 8 , 11 , 12 , 13 , 14 , 32 ]. Accordingly, the role of SP, NKA and their receptors was determined using two types of uterine strips.…”

“…Although both cholinergic and adrenergic components are primarily involved in controlling uterine function, other neurotransmitters have also been shown to be responsible for modulating uterine contractility. To date, the role of noradrenaline, acetylcholine (ACh), somatostatin, neuropeptide Y and galanin in the contractile regulation of the porcine uterus with the bacterially induced inflammation has been described [ 11 , 12 , 13 , 14 ].…”