The hypothalamo-pancreatic axis: evidence for a neurohormonal pathway in the control of the release of insulin and glucagon.

Segments of freshly dissected rat hypothalamic tissue corresponding to the ventrolateral (VLH) and ventromedial (VMH) regions were incubated in Gey and Gey medium at 37 C under 95% O2 and 5% CO2 for 30 minutes. Groups of male rats which had been fasted for 6 hours received injections (i.v.) of either VMH medium or VLH medium while a third group received control medium only. Blood samples were taken from the aorta 3 minutes post-injection and circulating levels of insulin and glucagon were determined by RIA. The medium from the incubation of the VMH tissue significantly elevated glucagon levels and significantly lowered plasma concentrations of insulin compared to the levels in animals receiving injections of control medium. The hormone levels in animals receiving an injection of medium in which VLH tissue had been incubated did not differ significantly from the controls. In another type of experiment VMH medium, but not VLH medium, was able to overcome the somatostatin-induced inhibition of glucagon release. These observations suggest that hypothalamic factors may be involved in the regulation of the endocrine pancreas.     

Regulation of ornithine decarboxylase by ODC-antizyme in HTC cells.

Low concentrations of putrescine (10^?5M) blocked ornithine decarboxylase (ODC) in rat hepatoma (HTC) cells in culture, but the lower homologue of putrescine, 1, 3 diaminopropane, had no effect on ornithine decarboxylase at 10^?5M. Higher concentrations of both putrescine and 1, 3 diaminopropane induced approximately the same amount of soluble ODC antizyme type inhibitor. When concentrated dialyzed supernatants of cells grown in 10^?5M putrescine were treated with 250 mM NaCl and chromatographed on a superfine Sephadex G-75 column, both ODC and inhibitor were recovered. Spermidine, spermine and cadaverine also induced the inhibitor suggesting a low specificity of induction by amines.     

Differential role of the opioid μ and δ receptors in the activation of prolactin (PRL) and growth hormone (GH) secretion by morphine in the male rat

Administration of naloxazone (50 mg/kg i.v.), an irreversible, selective and long acting antagonist of the μ₁ subclass of the opioid receptors, strongly reduced stimulation of PRL secretion by morphine (5.0 mg/kg i.v.) injected 24 hours later into conscious, unrestrained rats. In contrast, the effect of morphine on PRL release was unimpaired in rats treated 24 hours beforehand with either the reversible opioid antagonist naloxone (50 mg/kg i.v.), or the vehicle for naloxazone. A complete suppression of the PRL response to morphine (3.0 mg/kg i.v.) was observed in animals given intraventricular (IVT) injection of β-funaltrexamine (β-FNA, 2.5 μg), another selective, irreversible and long acting antagonist of the μ receptors, 24 hours beforehand. Neither naloxazone nor β-FNA had any effect on the activation of GH secretion by morphine, which, however, was conspiciously reduced by ICI 154, 129, a preferential δ receptor antagonist, injected IVT (50 μg) 5 minutes before morphine. It is concluded that the PRL stimulating effect of morphine is mediated by the μ receptors, wherease activation of GH probably involves the δ sites.     

Alterations in polyamine metabolism during embryonal carcinoma cell differentiation in vitro

Murine embryonal carcinoma (EC) cells can be stimulated to differentiate by several chemical inducers. Since the response of EC cells to induction is likely to occur shortly after exposure to the inducer, we report here the changes that occur in polyamine levels in a number of EC cell lines shortly after exposure to two chemical stimuli, alpha-difluoromethylornithine (DFMO) and retinoic acid (RA). Our results suggest that polyamine levels are important in determining the state of EC cell differentiation, but that reduction in these levels alone is not sufficient to induce differentiation in all the EC cell lines tested. Also, it is apparent that RA does influence levels of polyamines. However, this influence does not seem to be mediated through direct interaction with ODCase.     

Pressure-flow effects on endurance of inspiratory muscles

We examined the effects of varying inspiratory pressures and flows on inspiratory muscle endurance. Four normal subjects performed voluntary forced breathing with various assigned inspiratory tasks. Duty cycle, tidal volume, and mean lung volume were the same in all tasks. Mean esophageal pressure, analogous to a pressure-time integral (PTes), was varied over a wide range. In each task the subject maintained an assigned PTes while breathing on one of a range of inspiratory resistors, and this gave a range of inspiratory flows at any given PTes. Inspiratory muscle endurance for each task was assessed by the length of time the task could be maintained (Tlim). For a given resistor, Tlim increased as PTes decreased. At a given PTes, Tlim increased as the external resistance increased and therefore as mean inspiratory flow rate (VI) decreased. Furthermore, for a given Tlim, PTes and VI were linearly related with a negative slope. We conclude that inspiratory flow, probably because of its relationship to the velocity of muscle shortening, is an independent variable importantly influencing endurance of the inspiratory muscles.