Expression Patterns of PACAP and PAC1R Genes and Anorexigenic Action of PACAP1 and PACAP2 in Zebrafish

Abstract

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide with potent suppressive effects on feeding behavior in rodents, chicken, and goldfish. Teleost fish express two PACAPs (PACAP1, encoded by the adcyap1a gene, and PACAP2, encoded by the adcyap1b gene) and two PACAP receptors (PAC1Rs; PAC1Ra, encoded by the adcyap1r1a gene, and PAC1Rb, encoded by the adcyap1r1b gene). However, the mRNA expression patterns of the two PACAPs and PAC1Rs, and the influence and relationship of the two PACAPs on feeding behavior in teleost fish remains unclear. Therefore, we first examined mRNA expression patterns of PACAP and PAC1R in tissue and brain. All PACAP and PAC1Rs mRNAs were dominantly expressed in the zebrafish brain. However, adcyap1a mRNA was also detected in the gut and testis. In the brain, adcyap1b and adcyap1r1a mRNA levels were greater than that of adcyap1a and adcyap1r1b , respectively. Moreover, adcyap1b and adcyap1r1a mRNA were dominantly expressed in telencephalon and diencephalon. The highest adcyap1a mRNA levels were detected in the brain stem and diencephalon, while the highest levels of adcyap1r1b were detected in the cerebellum. To clarify the relationship between PACAP and feeding behavior in the zebrafish, the effects of zebrafish (zf) PACAP1 or zfPACAP2 intracerebroventricular (ICV) injection were examined on food intake, and changes in PACAP mRNA levels were assessed against feeding status. Food intake was significantly decreased by ICV injection of zfPACAP1 (2 pmol/g body weight), zfPACAP2 (2 or 20 pmol/g body weight), or mammalian PACAP (2 or 20 pmol/g). Meanwhile, the PACAP injection group did not change locomotor activity. Real-time PCR showed adcyap1 mRNA levels were significantly increased at 2 and 3 h after feeding compared with the pre-feeding level, but adcyap1b, adcyap1r1a , and adcyap1r1b mRNA levels did not change after feeding. These results suggest that the expression levels and distribution of duplicated PACAP and PAC1R genes are different in zebrafish, but the anorexigenic effects of PACAP are similar to those seen in other vertebrates.

Tracing the Origins of the Pituitary Adenylate-Cyclase Activating Polypeptide (PACAP)

“…In amphibian and fish (teleost and cartilaginous fish) brain PACAP is abundant and has a similar distribution to that in mammals and is predominantly expressed in the hypothalamic nuclei but also in other brain regions (Valiante et al, 2006;Vaudry et al, 2009). In the zebrafish that has duplicated adcyap1 genes, transcripts for adcyap1a are most expressed in the brain stem and diencephalon, while adcyap1b gene transcripts are abundant in the telencephalon and diencephalon (Nakamachi et al, 2019). Although, the distribution of PACAP is relatively well-characterized in fish, few studies have characterized the function of the teleost duplicate PACAPs.…”

Intranasal Administration of PACAP Is an Efficient Delivery Route to Reduce Infarct Volume and Promote Functional Recovery After Transient and Permanent Middle Cerebral Artery Occlusion

“…The anorexigenic effects of PACAP have mainly been studied in various species such as chickens ( 43 ), fishes ( 44 , 45 ), and rodents ( 46 , 47 ), using different routes of administration from systemic ones such as IV or IP to direct brain administrations such as ICV or amygdala central nucleus injections. In the present study the effect of IN administration of PACAP was evaluated on body weight variation and food intake.…”

“…However, most trials so far have failed, probably because molecules could only target part of stroke induced deleterious pathways. In this context, PACAP may be a promising molecule as it could counteract most if not all the deleterious processes induced by stroke and improve functional recovery in various MCAO models (39)(40)(41)(42)(43)(44)(45)(46)(47)(48). However, to consider the use of PACAP in clinic, several points remain to be evaluated and/or improved.…”

The Prominent Role of Pituitary Adenylate Cyclase-Activating Polypeptide in Spermatogenesis and Function of Spermatozoa: A Mini Review

“…PACAP is neuropeptide molecule [23,24,25] which expressed extensively in many tissue of the body [26]. PACAP and its receptor is not only express in hypothalamus, however it also expressed in more of the other peripheral organ [27].…”