Physiology and pathophysiology of hypocretins/orexins


Ten years ago a 33- and a 28-aminoacid peptide were discovered in the lateral hypothalamic area as hypocretin 1 or orexin A (OXA) and hypocretin 2 or orexin B (OXB) by two independent research teams. de Lecea and colleagues used a molecular biological approach isolating cDNA clones which were expressed in the hypothalamus but not in the cerebellum or hippocampus. One clone was exclusively expressed in the posterior hypothalamus coding for a putative secretory protein which gave rise to two peptides (de Lecea et al. 1998). They named the peptides according to their expression site (hypothalamus) and similarity to secretin, hypocretin-1 and -2. At the same time Sakurai et al. (1998) identified two peptides that were endogenous ligands to orphan receptor HFGAN72. They found that these peptides after i.c.v. injection stimulated food intake and their expression was upregulated upon fasting. Therefore, the group named these peptides ‘orexins’ after the Greek word ‘orexis’ meaning appetite. Both names are used in the scientific literature as it is done in this issue of Acta Physiologica.

Since the discoveries of hypocretins/orexins a large amount of data has been accumulated demonstrating their involvement in many physiological systems. The effects of hypocretins/orexins are best characterized in the central nervous system (CNS; Sakurai 2007) with their clinical relevance in narcolepsy (Bourgin et al. 2008). Recent evidence suggests that hypocretins/orexins might also have a role outside the CNS but the physiological relevance of hypocretins/orexins and their receptors in the periphery is still under investigation (Fig. 1) (Heinonen et al. 2008).

Figure 1.

 Effects of orexin A in peripheral tissues.↑: stimulation; ↓: inhibition; ↑↓: data for both stimulatory and inhibitory effects of orexin A (from Heinonen et al. 2008).

This issue of Acta Physiologica comprises a total of 20 articles (five regular and 15 state-of-the-art reviews) by the original discoverers in addition to leading research teams in the hypocretin/orexin field. The articles are developed from presentations and discussions given at the 16th Acta Physiologica International Symposium ‘10 Years of Hypocretins/Orexins – Physiology and Pathophysiology’ held at the University and Biocenter of Oulu, Finland, 13 to 14 August 2008. The articles are divided into three sections: I. Central nervous system, arousal, sleep and synaptic plasticity and locomotor behaviour. II. Peripheral effects of orexins. III. Zebra fish model, receptor signalling and cell function.

Dr Krister Stefan Eriksson (1963–2008) tragically died shortly after the meeting in which he served a as chairman on the scientific section sleep, arousal and addiction, and contributed an article to this issue. An obituary by Pertti Panula and Helmut Haas follows this editorial. We would like to dedicate this issue to him.


The meeting was kindly supported by the Foundation Nordisk Fysiologi, Oslo, Norway, and The Federation of Finnish Learned Societies, Finland. Furthermore, we are indebted to all members of the organization team and students, but in particular to Hannele Savela, PhD, and Johanna Issakainen, MSc, for their excellent support in all areas of the meeting.