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Biomedical subjects

G E Handelmann

Publications and source records attributed to G E Handelmann.

25 records · Page 2Linked to original sources

Behavioral effects of [4-norleucine, 7-D-phenylalanine]-alpha-melanocyte-stimulating hormone.

The behavioral effects of alpha-melanocyte stimulating hormone (alpha-MSH) were compared to an alpha-MSH analogue that had a norleucine substituted for methionine in the four position and a D-phenylalanine substituted for L-phenylalanine in the seven position. [Nle4, D-Phe7]-alpha-MSH has previously been shown to be a superpotent agonist on melanocytes [17]. The present experiments indicate that [Nle4, D-Phe7]-alpha-MSH is equipotent to alpha-MSH in inducing grooming when administered intraventricularly. In contrast, the analogue has the opposite effect of alpha-MSH on performance of a visual discrimination task. alpha-MSH improves visual performance whereas [Nle4, D-Phe7]-alpha-MSH attenuates such performance. The contrasting activities of [Nle4, D-Phe7]-alpha-MSH on the physiological processes described suggest that this analogue may interact with three distinct melanotropin receptors in different ways. On melanocyte receptors the melanotropin analogue is a superagonist, on CNS melanotropin receptors involved in grooming it is equipotent to alpha-MSH, and on CNS receptors involved in attention, learning and memory [Nle4, D-Phe7]-alpha-MSH may be an antagonist of endogenous melanotropin.

Animals↗

Secretin modulation of behavioral and physiological functions in the rat.

The effect of secretin on behavioral and physiological functions in the rat was investigated. Secretin injected intracerebroventricularly (ICV) significantly increased defecation and decreased novel-object approaches in rats. The peptide showed no significant effects on stereotypic behavior (gnawing, grooming and rearing), open-field locomotor activity however was significantly decreased, an effect that was probably due to a decreased propensity for the rats to initiate locomotor responses. In addition, secretin showed significant effects on respiration rate in anesthetized rats. When the peptide was injected in the lateral ventricle a decrease in respiration rate occurred, but when the brain was perfused from the lateral ventricle to the cisterna magna increases in respiration rate occurred. These data, combined with the facts that secretin and secretin receptors have been identified in the brain indicate that secretin may play a neurotransmitter or neuroregulator role in the central nervous system.

Animals↗

Vasopressin administration to neonatal rats reduces antidiuretic response in adult kidneys.

Neonatal rats who had been given injections of vasopressin on days 1-7 after birth exhibited polyuria as adults. In vivo antidiuresis bioassays demonstrated that their kidneys were deficient in their ability to concentrate urine in response to stimulation with vasopressin. The kidneys also showed a reduction in vasopressin-induced cyclic AMP production, although parathyroid hormone- and calcitonin-induced levels were normal. This suggests a specific deficit in vasopressin receptor-adenylate cyclase function. In contrast, the neonatal treatment had no effect on the sensitivity of the adult vasculature to the hypertensive effects of vasopressin. These results show that short exposures to high levels of vasopressin early in development can produce a long-term defect in vasopressin responsiveness that is specific to the kidney.

Animals↗

Alpha-melanocyte stimulating hormone facilitates learning of visual but not auditory discriminations.

The neuropeptide alpha-MSH has been proposed to influence learning and memory by increasing visual attention. To test the possibility that MSH selectively affects visual learning, rats were tested in learning tasks in which the cues were either visual or auditory. Maze and bar-press tasks were used. MSH administration increased the rate of learning of the visual tasks, regardless of the task difficulty or the type of response required of the rat. MSH had no effect on the rate of learning of the auditory tasks. These results support the hypothesis that MSH facilitates learning by influencing some aspect of visual information processing.

Acoustic Stimulation↗

Extra-hippocampal projections of CCK neurons of the hippocampus and subiculum.

A population of neurons in the hippocampus and subiculum contains cholecystokinin (CCK). Following transection of the dorsal fornix, a major afferent pathway of the hippocampus and associated structures. CCK levels were reduced in the septum and hypothalamus. A microdissection analysis indicated that the loss of CCK occurred in nuclei receiving direct projections from the hippocampus and subiculum, suggesting that CCK-containing neurons in the hippocampus and subiculum project to extrahippocampal regions.

Afferent Pathways↗

Neonatal exposure to vasopressin decreases vasopressin binding sites in the adult kidney.

Previous experiments showed that rats injected with vasopressin (AVP) during the first seven days after birth were less sensitive as adults to the antidiuretic effects of AVP than were control rats. In the present experiment, binding sites for AVP were measured in the kidneys of similarly treated adult rats. Neonatal exposure to AVP significantly decreased the number of binding sites in the adults, but did not affect the binding affinity of the sites. It is concluded that neonatal exposure to AVP which produces a long-lasting decrease in responsiveness of the kidney to AVP is correlated with a reduction in the number of AVP binding sites in the tissue.

Animals↗

Secretin receptors in the rat kidney: adenylate cyclase activation and renal effects.

In previous studies it has been demonstrated that pharmacological administration of secretin can alter urine output. Whether the effect is due to a direct action on kidney was investigated by examining the effect of secretin on renal output, and determining whether there were secretin receptors and a secretin sensitive adenylate cyclase in the kidney. Secretin had an antidiuretic action on kidney when administered intravenously to anesthetized hydrated rats. In addition, binding sites for (125I)-secretin, and a secretin sensitive adenylate cyclase were identified in rat kidney. Binding was saturable and reversable and was half maximally inhibited by 1 X 10(-7) M synthetic porcine secretin. Autoradiographic studies revealed a high density of secretin binding sites in the outer medulla of the kidney, a region that is composed mainly of the thick ascending limb of the loop of Henle, and is also the major site of action for the antidiuretic hormone, vasopressin. The data indicate that a functional secretin receptor system exists in kidney which may have a physiological role in regulating urine output.

Adenylyl Cyclases↗