Here, we characterised SK/CCK-type signalling for the first time inside a non-chordate deuterostome C the starfish (phylum Echinodermata). Availability StatementThe sequences of cDNAs encoding ArSK/CCKP and ArSK/CCKR have been deposited PS 48 in GenBank under accession figures, “type”:”entrez-nucleotide”,”attrs”:”text”:”KT601716″,”term_id”:”940373966″,”term_text”:”KT601716″KT601716 and “type”:”entrez-nucleotide”,”attrs”:”text”:”MW261740″,”term_id”:”2057274919″,”term_text”:”MW261740″MW261740, respectively. All PS 48 data generated or analysed during this study are included in the manuscript and assisting documents. Source data files have been offered for Numbers 1,2,3,7,8 and 9. The following dataset was generated: Semmens DC, Mirabeau O, Moghul I, Pancholi MR, Wurm Y, Elphick MR. 2016. Asterias rubens cholecystokinin-type precursor, mRNA, total cds. NCBI GenBank. KT601716 Tinoco Abdominal, Barreiro-Iglesias A, Ya?ez Guerra LA, Delroisse J, Zhang Y, Gunner EF, Zampronio CG, Jones AM, Egertova M, Elphick MR. 2021. Asterias rubens cholecystokinin-type receptor (CCKR) mRNA, total cds. NCBI GenBank. MW261740 Abstract Sulfakinin (SK)/cholecystokinin (CCK)-type neuropeptides regulate feeding and digestion in protostomes (e.g. bugs) and chordates. Here, we characterised SK/CCK-type signalling for the first time inside a non-chordate deuterostome C the starfish (phylum Echinodermata). With this varieties, two neuropeptides (ArSK/CCK1, ArSK/CCK2) derived from the precursor protein ArSK/CCKP act as ligands for an SK/CCK-type receptor (ArSK/CCKR) and these peptides/proteins are indicated in the nervous system, digestive system, tube ft, and body wall. Furthermore, ArSK/CCK1 and ArSK/CCK2 cause dose-dependent contraction of cardiac belly, tube foot, and apical muscle mass preparations in vitro, and injection of these neuropeptides in vivo causes cardiac belly retraction and inhibition of PS 48 PS 48 the onset of feeding in (Nachman et al., 1986a). Subsequently, GPCRs that are homologs of the vertebrate CCKA/CCKB-type receptors have been recognized and pharmacologically characterised as receptors for sulfakinin (SK)-type peptides in a variety of bugs, including (Bloom et al., 2019; Kubiak et al., 2002; CAB39L Yu et al., 2013b; Yu and Smagghe, 2014b). Furthermore, investigation of the physiological tasks of SK-type signalling in bugs has revealed similarities with findings from vertebrates. Thus, in several insect species SK-type peptides have myotropic effects around the gut (Al-Alkawi et al., 2017; Marciniak et al., 2011; Nachman et al., 1986a; Nachman et al., 1986b; Nichols, 2007; Palmer et al., 2007; Predel et al., 2001; Schoofs et al., 1990) and/or impact digestive enzyme release (Harshini et al., 2002a; PS 48 Harshini et al., 2002b; Nachman et al., 1997; Zels et al., 2015). Furthermore, at a behavioural level there is evidence that SK-type peptides act as satiety factors (Al-Alkawi et al., 2017; Bloom et al., 2019; Downer et al., 2007; Maestro et al., 2001; Meyering-Vos and Mller, 2007; N?ssel and Zandawala, 2019; Nichols et al., 2008; Wei, 2000; Yu et al., 2013a; Yu et al., 2013b; Yu and Smagghe, 2014b; Zels et al., 2015) and regulate locomotion and aggression in insects (Chen et al., 2012; N?ssel and Williams, 2014; N?ssel and Zandawala, 2019; Nichols et al., 2008). The discovery and functional characterisation of SK-type signalling in insects and other arthropods indicated that this evolutionary origin SK/CCK-type signalling can be traced back to the common ancestor of the Bilateria. Consistent with this hypothesis, SK/CCK-type signalling systems have been discovered in a variety of protostome invertebrates, including the nematode and the annelid (Janssen et al., 2008; Mirabeau and Joly, 2013; Schwartz et al., 2018). Furthermore, some insights into the physiological functions of SK/CCK-type signalling in non-arthropod protostomes have been obtained, including causing a decrease in the frequency of spontaneous contractions of the hindgut (Schwartz et al., 2018), activation of digestive enzyme secretion in and (Nachman et.