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  • Although the role of apelin and APJ

    2023-03-16

    Although the role of apelin and APJ receptor in cardiovascular functions has been well-elucidated, little is known for the effect of the central apelinergic system on gastrointestinal (GI) functions. In mice, it has been found previously that central exogenous apelin-13 decreased gastric emptying (GE), GI transit rate (Lv et al., 2011) and distal colonic transit (Yang et al., 2010). In addition, we have found previously that APJ receptor is expressed in stomach-projecting DMV neurons, furthermore, apelin-induced gastroinhibitory action was abolished by truncal vagotomy suggesting that central apelin may regulate parasympathetic outflow by altering vagal efferent signaling (Birsen et al., 2016; Bulbul et al., 2018). On the other hand, intra-RVLM application of apelin-13 was shown to increase TAK-285 rate, arterial pressure and renal sympathetic nerve activity in rats (Masaki et al., 2012; Seyedabadi et al., 2002; Yao et al., 2011; Zhang et al., 2009) raising the possibility that central apelin inhibits gastric motor functions via activating sympathetic outflow in addition to its suppressor action on vagal parasympathetic signaling. However, the relevant mechanism has not been investigated. Neurons within the RVLM directly project to the sympathetic preganglionic neurons within the intermediolateral (IML) column of the spinal cord to regulate sympathetic outflow to the viscera (Badoer, 2001; Browning and Travagli, TAK-285 2014). In rats, it was demonstrated previously that central administration of corticotropin-releasing factor (CRF) as well as acute restraint stress loading inhibited solid GE by disturbing the coordination of postprandial antro-pyloric contractions through peripheral α-2 adrenergic receptor-mediated sympathetic pathway (Nakade et al., 2005; Nakade et al., 2006).
    Materials and methods
    Results In vehicle-injected control rats, solid GE was measured 61.9% ± 4.3 (n = 6), whereas it was delayed significantly (39.9% ± 6.7, n = 7, p < 0.05) in rats received central apelin-13 administration (30 nmol, icv) (Fig.1). To better clarify the inhibitory effect of central apelin-13 on GE, the coordinated antro-pyloric contractions of gastric fed motor pattern was recorded in conscious freely-moving rats. The representative postprandial antro-pyloric contractions occurred following ingestion of a solid pellet are shown in Fig.2. In rats fasted overnight, immediately after initiation of feeding, spontaneous contractions were observed in both antrum and pylorus. Approximately 30 min after feeding, the coordinated antro-pyloric contractions were recorded. Apelin-13 administration (30 nmol, icv) inhibited the spontaneous contractions remarkably both in antrum and pylorus (Fig.2A), while impairing the antro-pyloric coordination (Fig.2B). MI was calculated as AUC in 30 min period before and after each injection. The changes in MI were expressed as % of pre-injection period. Compared to the vehicle, apelin-13 administration decreased MI significantly both in antrum and pylorus, however, this effect was more prominent in antrum (p < 0.01) compared with pylorus (p < 0.05) (Fig.3). To clarify the central autonomic pathways involved in its gastroinhibitory action, apelin-13 was injected in rats previously underwent CGX and/or subdiaphragmatic truncal VGX. In sham-operated rats, solid GE was 62.8% ± 4.4 (n = 7) which was decreased significantly in rats received central administration of apelin-13 (29.5% ± 4.8, n = 7, p < 0.05). CGX did not change solid GE (64.1% ± 3.1, n = 6), while VGX itself caused a slight decrease in GE (41.1% ± 4.2, n = 6, p < 0.05). The apelin-induced delayed GE was attenuated partially in rats underwent CGX (40.3% ± 6.8; p < 0.05, n = 8) and VGX (49.7% ± 3.5; p < 0.05, n = 8), whereas it was restored completely in CGX + VGX animals (54.8% ± 3.8; p < 0.01, n = 7), (Fig.4).