On the blood-brain barrier to peptides: effects of immobilization stress on regional blood supply and accumulation of labelled peptides in the rat brain.

Tritiated arginine-vasopressin (AVP), desglycinamide-vasopressin (DGAVP), chicken gonadotropin releasing hormone (GnRH) or carbetocin were injected intracarotidally into rats exposed to a restraint stress for 60 min. The peptide accumulations were determined in 9-13 brain regions and anterior pituitary. In separate experiments the cerebral blood flow was measured.

New reduced peptide bond substance P agonists and antagonists: effects on smooth muscle contraction.

Following the recent discovery of a new substance P (SP) competitive pancreatic acini cell receptor antagonist containing a reduced peptide bond in place of the C-terminal peptide bond, a new series of full chain and short chain (heptapeptide and hexapeptide) substance P analogues have been prepared in which one of the C-terminal-region peptide bonds has been replaced by CH2NH or CH2O groups. They were compared for their ability to recognize NK1 and/or NK2 tachykinin receptor binding sites on guinea pig ileum and rat duodenum smooth muscle preparations, respectively. It was found that all full sequence SP pseudopeptides were agonists with much reduced bioactivity in both tested systems and, in addition, [Gly9 psi(CH2NH)Leu10,Leu11]SP was found to be a relatively selective agonist for NK1 binding sites.

Tritiation of [8-L-arginine, 9-desglycineamide] vasopressin.

Tritiated vasopressin analogue, [8-L-arginine, 9-desglycineamide]-vasopressin was prepared from its diiodo-derivative by means of catalytic reductive dehalogenation. The reaction products were purified by reversed-phase HPLC resulting in a labelled peptide with high specific radioactivity (629 TBq/mmol).

The effect of AVP and DGAVP on the exploratory activity of rats.

The effects of [8-L-arginine] vasopressin (AVP) and desglycinamide [8-L-arginine] vasopressin (DGAVP) were tested on the exploratory activity of adult male rats in a novel environment. The inherited individual differences in the non-specific excitability level of the animals were ascertained prior to the drug administration and the rats were then distributed evenly into the experimental groups. One half of each groups contained the less excitable and the other the more excitable animals.

On the blood-brain barrier to peptides: accumulation of labelled vasopressin, DesGlyNH2-vasopressin and oxytocin by brain regions.

After intracarotid injection of 125I-arginine vasopressin (AVP), 125I- or 3H-lysine vasopressin (LVP), 3H-DesGlyNH2-arginine vasopressin (DGAVP), and 125I- or 3H-oxytocin (OXT), the accumulation of radioactivity was determined in 13 to 18 brain regions and anterior pituitary in rats. Calculated extraction by tight capillary regions amounts to about 1-2% independently of the peptide doses injected (4 X 10(-4) to 5 X 10(-9) mol-1). This indicates a low but measurable extraction of labelled peptides which furthermore is nonsaturable.