Separation of canavanine and canaline by high performance liquid chromatography

The plant amino acid canavanine and its hydrolytic product canaline were successfully separated and identified by Reverse Phase High Performance Liquid Chromatograph (RP-HPLC). This procedure was used to demonstrate the arginase-mediated cleavage of canavanine to yield canaline and urea, and the subsequent formation of a Schiff's base complex between canaline and pyridoxal phosphate. Both aforementioned reactions were demonstrated by RP-HPLC.     

Rapid development of tolerance to the behavioural actions of cholecystokinin

Cholecystokinin (CCK) acts acutely to inhibit food consumption in fasted rats, mice, sheep, pigs, monkeys and humans. CCK has been proposed as a satiety signal, inducing the behavioural sequence of satiety, or as an aversive internal stimulus, which inhibits food intake by inducing malaise. Reductions in food intake and related exploratory behaviours are initiated by CCK at its peripheral receptor in the gut, which appears to transmit sensory feedback via the vagus nerve to brain regions mediating appetitive behaviours. The therapeutic potential of CCK as an appetite suppressant in obesity syndromes rests on the demonstration of significant, long-lasting body weight reduction. Chronic CCK administration by repeated injections is problematic, since this peptide is rapidly degraded in vivo. We chose the Alzet constant infusion osmotic minipump to investigate possible alterations in body weight and food intake during continuous infusion of CCK. We now report that no change was detected in either body weight or total daily food consumption at any time point during 2 weeks of intraperitoneally (i.p.) infused CCK. The mechanism underlying the lack of chronic CCK effects appears to be a rapid development of behavioural tolerance. Acute challenge doses of CCK which induced satiety-related behaviours in saline-infused rats were ineffective in CCK-infused rats. The behavioural tolerance was apparent within a few hours of minipump implantation. These results provide the first evidence that rapid and reversible tolerance develops to the actions of a gut peptide.     

A simple system of multiple organ-baths

Summary A compact and easily assembled system of multiple organ-baths is described, in which use is made of readily available materials.Acknowledgment. G.E.R. was in receipt of the ruggles Gates Research Award.     

Inhibitory effect of cytokinins on PHA-induced human lymphocyte stimulation

Summary The inhibitory effect of various purine derivatives on PHA-induced human lymphocyte blast formation was studied. Two nucleoside cytokinins, N⁶-benzyladenosine and N⁶-isopentenyladenosine, inhibited blast formation at concentrations as low as 10^–6 M. However, the other cytokinins, which lacked the ribosyl residue at N⁹ position, had to be at the higher molar concentration of 10^–4 before they could induce the same inhibitory effect.     

Long term stability of lysine vasopressin and of specifically tritiated lysine vasopressin in weakly acidic aqueous solutions

Summary Lysine vasopressin tritiated at meta position of tyrosine (1.9 Ci/mmole) decomposes during a long storage period, mainly as a result of radiolysis. The loss of specific activity by isotopic exchange with water is slow. The nonlabelled peptide undergoes only very minute decomposition (polymerization). Specific radioactivity declines with a half life of 47.4 months.Acknowledgments. This research was supported by Swiss National Science Foundation, grant No.3.040.76 (V.P.). Some of the measurements (years 1969–70) were carried out at Roche Institute of Molecular Biology, Nutley, N.J., USA.     

Permeability of fresh and stored human erythrocytes to glycerol and its acylated derivatives

Summary The effect of copper ions on the permeation of glycerol and its mono-, di-, and triacetate derivatives was studied in fresh and stored erythrocytes. Permeability was unchanged with storage. Acylated glycerols permeate the cells mainly by non-facilitated mechanism, as their transport is almost unaffected by copper ions.Portions of this work were included in the graduate thesis of Dr. Yaeger in partial fulfillment of the requirements for the M. D. degree.Acknowledgement. We thank Mrs Dalia Mazor for expert technical assistance.     

The effect of postnatal undernourishment on epileptiform kindling of dorsal hippocampus

Summary Rats were undernourished postnatally from birth through 20 days of age. They were subsequently tested for susceptibility to motor seizures kindled in hippocampus in adulthood. Compared to littermate control animals the postnatally undernourished rats were more susceptible to the kindling treatment. We conclude that early postnatal undernourishment has a permanent effect on susceptibility of the hippocampus to electrically-induced seizures.This work was supported by Public Health Service grant NS 13799, National Science Foundation grant GB 35532, and by Hoffman-LaRoche, Inc.