Area postrema, a brain circumventricular organ, is the site of antidipsogenic action of circulating atrial natriuretic peptide in eels

Abstract

SUMMARY Accumulating evidence indicates that circulating atrial natriuretic peptide(ANP) potently reduces excess drinking to ameliorate hypernatremia in seawater(SW) eels. However, the cerebral mechanism underlying the antidipsogenic effect is largely unknown. To localize the ANP target site in the brain, we examined the distribution of ANP receptors (NPR-A) in eel brain immunohistochemically using an antiserum specific for eel NPR-A. The immunoreactive NPR-A was localized in the capillaries of various brain regions. In addition, immunoreactive neurons were observed mostly in the medulla oblongata, including the reticular formation, glossopharyngeal-vagal motor complex, commissural nucleus of Cajal, and area postrema (AP). Trypan Blue, which binds serum albumin and does not cross the blood–brain barrier, was injected peripherally and stained the neurons in the AP but not other NPR-A immunopositive neurons. These histological data indicate that circulating ANP acts on the AP, which was further confirmed by physiological experiments. To this end, the AP in SW eels was topically destroyed by electric cauterization or were by chemical lesion of its neurons by kainic acid, and ANP (100 pmol kg–1) was then injected into the circulation. Both heat-coagulative and chemical lesions to the AP greatly reduced an antidipsogenic effect of ANP, but the ANP effect was retained in sham-operated eels and in those with lesions outside the AP. These results strongly suggest that the AP, a circumventricular organ without a blood–brain barrier, serves as a functional window of access for the circulating ANP to inhibit drinking in eels.

The response of non-traditional natriuretic peptide production sites to salt and water manipulations in the rainbow trout

“…Results from eel NP studies have primarily led to the osmoregulatory theory for the NP system. The central point of inference in the NP osmoregulatory hypothesis is that an elevated plasma osmolarity acts as a stimulus for cardiac NPs ( potent antidipsogen and inhibits sodium appetite in the brain (Tsukada et al, 2007). However, an alternative interpretation of eel NP studies could also support a volume-responsive system.…”

“…In tilapia, a role for NPs in the stimulation of prolactin and growth hormone in the anterior pituitary has been established in vitro (Fox et al, 2007), and NPR-A mRNA has been found in most regions of the eel brain, including olfactory bulb, telencephalon, optic tectum, cerebellum and medulla oblongotta (Tsukada et al, 2007). However, the physiological role of centrally produced NPs in fish is still largely unknown.…”

The area postrema in hindbrain is a central player for regulation of drinking behavior in Japanese eels

“…However, these sensory circumventricular organs (CVOs) have not been anatomically identified in fishes. Evans blue dye injected intraperitoneally did not stain loci comparable to the SFO and OVLT in eels (31,44) but stained the AP, another CVO located in the distal end of the medulla oblongata, indicating the lack of BBB in this region. The AP is a possible site of action of circulating hormones in eels for the following reasons: 1) eels without the forebrain and midbrain drink normally during SW adaptation (10) and in response to peripheral ANG II (35); 2) ANG II and ANP injected into the fourth ventricle near the AP exerted dipsogenic and antidipsogenic actions, respectively, in eels (24); and 3) AP lesioning diminished the antidipsogenic action of ANP injected peripherally (44).…”

“…These hormones would have access to the brain loci located outside the blood-brain barrier (BBB), and the signals would then be transmitted via the neural network that regulates swallowing, the final step of drinking behavior. However, little is known in teleosts about the site of action of circulating hormones, the exception being the action of ANP on the area postrema (AP) located in the medulla oblongata (44).…”

“…Accumulating evidence suggests that the AP may be an important regulatory site that integrates drinking behavior in teleost fishes; however, thus far only ANP has been shown to have an effect on the AP (44). The aim of this study is to evaluate the role of the AP in regulation of drinking induced by various stimuli.…”