Commercially available preparations of natural porcine glucose-dependent insulinotropic polypeptide (GIP) were subjected to reverse phase HPLC. The material was found to give rise to 4 peaks which were characterized by HPLC-retention time and N-terminal sequence analysis. They represented: intact porcine GIP(1-42), 58% (wt/wt); the GIP-fragment des-tyr-ala-GIP(3-42), 32% (wt/wt); cholecystokinin (CCK)-33 2% (wt/wt); CCK-39 2% (wt/wt). HPLC-pure GIP(1-42) stimulated insulin release in rat isolated pre-cultured pancreatic islets in the presence of 16.7 mM glucose up to 240% vs. control, whereas the fragment des-tyr-ala-GIP(3-42) did neither increase insulin release nor exhibit antagonistic activity to GIP(1-42) at 100 ng/ml. These results indicate that commercially available porcine GIP-preparations may contain the biologically inactive des-tyr-ala-GIP(3-42) in high amounts, and in addition may be contaminated by CCK-peptides. HPLC-characterization of these peptide preparations prior to any biological study is crucial.

1. Postganglionic neurones supplying hairless and hairy skin of the cat hindlimb were analysed for their responses to thermal stimuli applied to the anterior hypothalamus and spinal cord in anaesthetized and artificially ventilated cats. Activity was recorded from multi-and single-unit bundles which were isolated from peripheral nerves. The neurones were functionally identified as cutaneous vasoconstrictor (CVC) and muscle vasoconstrictor (MVC) neurones. Activity in sudomotor (SM) neurones was either monitored indirectly by recording the phasic negative deflections of the skin potential from the surface of the hairless skin, or in some experiments additionally by recording activity directly from the SM axons. 2. The activity in forty-one out of forty-four multi-unit and six out of six single-unit CVC bundles was inhibited, in a graded manner, by hypothalamic warming. An increase in the temperature of the surface of hairless skin followed the decrease in activity of the CVC neurones supplying it. Large changes in skin temperature only followed decreases in CVC activity of more than 40%. Cooling of the hypothalamus had only weak transient effects on CVC neurones. 3. Simultaneous warming of hypothalamus and spinal cord had multiplicative effects on the activity in CVC neurones. Subthreshold warming of one structure increased the response to warming of the other one and reduced the threshold temperature. 4. SM neurones were not affected by hypothalamic warming, but activated during hypothalamic cooling. 5. MVC neurones were weakly activated during hypothalamic warming only if arterial blood pressure decreased, otherwise they were unaffected. It is likely that this activation was due to secondary unloading of arterial baroreceptors. 6. Two silent postganglionic neurones projecting to skin were activated during hypothalamic warming. These neurones may have had a vasodilatory function. 7. Rhythmicity of the activity in CVC neurones, related to the cycle of artificial ventilation, increased during hypothalamic warming whereas that of MVC neurones was unchanged. 8. The functionally highly specific responses to hypothalamic warming in CVC neurones indicate a pathway from the hypothalamus that is specific for CVC neurones, in contrast to MVC and SM neurones. This central pathway is integrated with other spinal and supraspinal reflex pathways that determine the characteristic reflex pattern of CVC neurones to somatic and visceral stimuli and possibly with pathways that generate other physiological changes during hypothalamic warming (e.g. increase in respiratory drive).Most neurones of the sympathetic outflow to skin and reciprocal fashion in the anaesthetized animal, although a skeletal muscle of the cat hindlimb have vasoconstrictor minority of cutaneous vasoconstrictor (CVC) neurones functions and exhibit distinct reflexes to stimulation of behave like muscle vasoconstrictor (MVC) neurones. These cutaneous receptors, visceral receptors, arterial discharge patterns depend on the integration of spinal and baroreceptors and...

No abstract

No abstract

SUMMARY1. We monitored sweat secretion (using skin potential) and blood flow (using skin temperature) in the hind-paw skin of chloralose-anaesthetized cats pre-treated with guanethidine, and studied the responses to electrical stimulation of the ipsilateral lumbar sympathetic trunk.2. Stimulation caused sweat secretion and an increase in skin blood flow which was almost entirely restricted to the paw pads and was completely ipsilateral. Stimulation of the tibial nerve trunk produced similar effects, except that the increase in blood flow was more prolonged.3. The vasodilator effect of sympathetic trunk stimulation was not affected by chronic deafferentation of the paw.4. Atropine methonitrate (05-1 mg/kg i.v.) abolished the sudomotor response to sympathetic stimulation, but did not attenuate the blood flow response.5. Hexamethonium (1-2 mg/kg i.v.) abolished the vasodilator response to sympathetic stimulation, but did not affect the sudomotor response. Larger doses of hexamethonium (10-20 mg/kg) abolished both responses.6. The data suggest that the lumbar post-ganglionic neurones mediating vasodilatation in the skin of the cat paw pad are distinct from those that mediate sudomotor secretion.