According to this preliminary observation, high densities of intraepithelial gammadelta+ T cells and a significantly elevated gammadelta+/CD3+ ratio are associated with untreated FA. If seen LNH in a gastroduodenoscopy and/or increased densities of gammadelta+ T cells in the biopsy specimen, the possibility of gastrointestinal FA should be reliably assessed by a food challenge.

We used the secretion of the novel salmon cardiac peptide (sCP) as a model to examine the mechanisms of ventricular hormone release. Mechanical load increased dose dependently the secretion of immunoreactive sCP from isolated perfused salmon ventricle, with 3. 3-fold increase when a load of 13 cmH(2)O was applied. Endothelin-1 (5 nmol/l) was also able to rapidly increase the secretion of sCP. The released peptide corresponded to the biologically active sCP-29, whereas the large ventricular storage consisted of pro-sCP-sized material. With the use of immunoelectron microscopy, a large number of granules containing immunoreactive sCP could be detected in salmon ventricle. As judged by RNA blot analysis, there was very active basal expression of the sCP gene in the ventricle, which was not increased by mechanical load of up to 2-h duration. Our results show that the ventricle actively expresses the gene of sCP, stores the prohormone in secretory granules, and releases the peptide in response to mechanical load and endothelin-1. Thus the salmon ventricle uses the regulated pathway to produce and release a hormone structurally related to the mammalian natriuretic peptides.

Mechanisms acting against accumulation of volume are important in pathophysiological situations with volume and salt overload, such as congestive heart failure. Osmoregulating animals that migrate between environments with high and low salinity are ideal models for studying the defence mechanisms against volume gain. We have now cloned and sequenced from salmon (Salmo salar) a cDNA encoding a novel vasorelaxant cardiac hormone of 29 amino acids which is produced by proteolytic processing of a 148-residue preprohormone. Structural and biological results, as well as its distribution indicate that it belongs to an unrecognized family related to natriuretic peptides, perhaps representing an ancestor of ANP and BNP. We have synthesized the 29-amino acid hormone and set up a specific radioimmunoassay. The distribution of the mRNA and peptide is strictly restricted to the heart, with high levels both in the atrium and ventricle in various fish species. The hormone relaxes aortic smooth muscle derived from salmon at nanomolar concentrations. Its release from isolated perfused salmon ventricle is very sensitive to mechanical load: a 10 mmHg load induces a rapid 5-fold increase in hormone release. Our results indicate that the novel cardiac hormone has an important role in fish volume regulation. They also demonstrate that mechanical stimuli have been central to volume regulation since early evolution.

The natriuretic peptide system plays a major role in the fluid and electrolyte homeostasis in vertebrates, based on results from physiological studies (reviewed in Ruskoaho, 1992;Thibault et al. 1999) and experiments with transgenic animals (John et al. 1995;Lopez et al. 1995;Matsukawa et al. 1999). The regulation of the synthesis and secretion of cardiac A-and B-type natriuretic peptides, is, however, still incompletely understood. The ability of salmon (Salmo salar) to maintain volume and electrolyte balance despite the highly challenging osmoregulatory conditions of sea and fresh water prompted us to use it as a model for our studies on the regulation of natriuretic peptides. As an initial step, we recently cloned and sequenced from salmon heart the cDNA of a novel peptide hormone, salmon cardiac peptide (sCP) (Tervonen et al. 1998), which is stored in secretory granules and released by mechanical load, analogous to the mammalian natriuretic peptides (Kokkonen et al. 2000). Homologues of the novel peptide can be found in several teleost species . The evolutional position of fish make them ideal for studying the conserved characteristics of the natriuretic peptide system (Powers, 1989;Postlethwait et al. 1998;Wittbrot et al. 1998). They also make excellent models for studies on the general factors regulating the expression and secretion of natriuretic peptides. In keeping with this we have recently found that the promoter of the sCP gene is very active not only in salmon heart but also in mammalian cardiomyocytes, suggesting that, despite the large phylogenetic distance, the same transcription factors are responsible for the heart-specific expression of the peptides in mammals and salmon (MajalahtiPalviainen et al. 2000). Since sCP transcripts or peptide cannot be found in any tissues outside the heart (MajalahtiPalviainen et al. 2000) it can be used as a specific model for the endocrine function of the heart.In fish and other ectothermic animals, thermal balance is governed by external sources of heat, and therefore ambient temperature has a major influence on most physiological processes. Many fishes are exposed seasonally to considerable changes in water temperature. Temperature acclimation is accompanied with compensatory changes in metabolic, contractile and morphological properties of muscle, which significantly offset the negative impact of Temperature has a major influence on cardiac natriuretic peptide in salmon 1. Natriuretic peptides have a major role in fluid and electrolyte homeostasis in vertebrates. Ambient temperature has a major influence on physiological processes in ectothermic animals.Here we have studied the mechanisms of regulation of a natriuretic peptide, sCP (salmon cardiac peptide), in salmon (Salmo salar) acclimatised and acclimated to varying temperatures.2. The circulating and cardiac levels of sCP were found to be markedly upregulated in warmacclimatised and warm-acclimated salmon. The release of sCP from isolated in vitro perfused salmon ventricle was, however, not increased by ...

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