Pituitary adenylate cyclase activating polypeptide (PACAP) was first isolated from ovine hypothalamus as two molecular forms, the basic 38 residue amidated peptide PACAP-38 and the N-terminal 27 amino acid sequence PACAP-27. A dense plexus of PACAP immunoreactive fibres is present in the internal and external layers of the median eminence and in other parts of the hypothalamus with PACAP cell bodies in the paraventricular and supraoptic nuclei. The present study shows, for the first time, that, as assessed by radioimmunoassay of extracted plasma, the amount of PACAP-38 in hypophysial portal is significantly greater than in peripheral blood, and that as assessed by reversed phase high performance liquid chromatography, PACAP 1-38 is the major form in portal blood. This evidence is crucial for the fact that PACAP-38 may be a hypothalamic-pituitary regulatory factor.

SUMMARY1. An operation on dogs for the implantation ofguide tubes to the lateral ventricle and cisterna magna and a method whereby the ventricular space can be repeatedly perfused in conscious and unrestrained animals are described.2. The characteristics of a recirculatory perfusion system were examined and the bulk formation and absorption of cerebrospinal fluid and the volume of the ventricular space perfused were derived from the concentrations achieved during the infusion of inulin into the system. 3. 5-hydroxyindol-3-ylacetic acid (5-HIAA), the acid metabolite of 5-hydroxytryptamine, and 3-methoxy-4-hydroxyphenylacetic acid (HVA), the main acid metabolite of dopamine, were demonstrated to be mainly removed from cerebrospinal fluid (c.s.f.) by an active transport system localized in the region of the fourth ventricle. 4. It was possible to inhibit the active transport of these acids from cerebrospinal fluid by pre-treating the dogs with probenecid.

The steroid anaesthetic Althesin (Glaxo), which is a mixture of two C21 steroids, alphaxalone (3 alpha-hydroxy-5 alpha-pregnane-11, 20-dione--the active compound) and alphadolone acetate (21-acetoxy-3 alpha-hydroxy-5 alpha-pregnane-11, 20-dione), has been especially useful for the study of forebrain-autonomic and neuroendocrine functions. As determined by the loss of the righting reflex, Child et al. found no sex difference in the anaesthetic dose of Althesin administered intravenously (i.v.). However, in our neuroendocrine studies in which the anaesthetic was administered intraperitoneally (i.p.) and at dosage sufficient to produce surgical anaesthesia and analgesia, we observed a sex difference in the efficacy of Althesin. This may explain the difficulties that have been encountered in obtaining adequate anaesthesia (blockade of the somatomotor response to pain) with Althesin. Here we report, using cortical electroencephalography, that Althesin is a more potent anaesthetic than either sodium pentobarbitone or urethane, and that anaesthesia in the male rat requires about four times more Althesin (administered i.p.) than in the female. This sex difference is age dependent, can be abolished by administering oestrogen to the male, does not depend on sexual differentiation of the brain, and cannot be attributed to a sex difference in the metabolic clearance rate of alphaxolone. These results, taken together with those of Richards and Hesketh, suggest that the effect of alphaxalone may be mediated by interactions with synaptic membranes that are more specific than simply a generalized change in membrane structure, and that these interactions are affected by sex steroids.

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