Characterization of a morphine-modulating peptide, FLFQPQRFamide, in the rat hypophysis: biochemical and immunocytochemical studies.

The octapeptide FLFQPQRFamide (F8Fa) is a FMRFamide-like peptide with a certain number of antiopiate properties. Previous studies have shown that both F8Fa specific receptors and F8Fa-like material are present in the rat central nervous system. In this study, RIA revealed that the rat neurohypophysis also contains F8Fa immunoreactive (IR) material (230 +/- 49 pg/neural lobe). HPLC profiles revealed several forms of F8Fa IR. Neurohypophysis extracts can also inhibit the binding of F8Fa to rat spinal cord preparations, which suggests that this F8Fa-like material has a biological activity. Immunocytochemical observations, at the light and electron microscopic levels, confirmed the presence throughout the neural lobe of F8Fa IR, in axonal fibers and terminals similar to those containing the more classical neurohypophysial hormones. Immunogold staining showed that F8Fa IR was restricted to neurosecretory granules in certain axonal and terminal profiles. Double staining of the same ultrathin sections, using our anti-F8Fa antiserum and vasopressin or its neurophysin specific antibodies, revealed that F8Fa IR was colocalized with vasopressin. F8Fa IR was not visible in ocytocinergic fibers or terminals. A striking depletion of F8Fa IR (80%) was observed in rats which were given 2% saline to drink for 6 days. Similarly, an ip injection of an hypertonic saline solution was shortly followed by a 20% drop of F8Fa IR. In vitro F8Fa IR release from isolated neurohypophysis was evoked under a 56 mM KCl depolarization. These results suggest that F8Fa IR may act as a paracrine/endocrine mediator released from the rat neurohypophysis.