Changes in substance P and somatostatin in the spinal cord after traumatic spinal injury in the rat

Immunoreactive substance P (SPI) and somatostatin (SOMI) are found in spinal cord but their physiological roles remain speculative. Several classes of neuropeptides, including endogenous opioids and thyrotropin-releasing hormone (TRH), have been implicated in the pathogenesis or recovery from spinal cord injury. In the present studies, changes in SPI and SOMI were examined in the spinal cord after traumatic injury in the rat. Both peptides showed time-dependent, localized decreases at the injury site, which were statistically related to the degree of post-traumatic neurological dysfunction. Such changes differ from those of a number of other peptides after spinal injury and suggest that substance P and/or somatostatin may play a role in the secondary pathophysiological responses which follow trauma to the spinal cord.     

Cholecystokinin releases β-endorphin from the anterior pituitary gland

The effect of cholecystokinin on the release of β-endorphin immunoreactivity from anterior pituitary quarters and from cultures of dispersed anterior pituitary quarters was investigated. Cholecystokinin (> 10⁻⁷ M) caused a slight release of β-endorphin immunoreactivity from the pituitary quarters only.It is concluded that the direct effect of cholecystokinin on the anterior pituitary is not likely to have a functional significance in the release of β-endorphin and the co-secreted ACTH.     

Substance P in the adrenal gland: Origin and species distribution

Substance P-like immunoreactivity (I-SP) was found in adrenal glands of cat, rabbit, guinea-pig, rat, cattle and man, as well as in a pheochromocytoma. I-SP was reduced in chronically denervated adrenal glands of rats and in adrenal glands of guinea-pigs pretreated with capsaicin, suggesting innervation of the adrenal glands by I-SP containing nerves, possibly of sensory origin. I-SP could partially be recovered from the chromaffin granule fraction of bovine adrenal medulla and a pheochromocytoma tumor. HPLC analysis of bovine chromaffin granules and a pheochromocytoma extract showed that the measured immunoreactivity corresponded to authentic substance P. Therefore, a dual localization of I-SP in nerve fibers and chromaffin cells can be assumed. The presence of somatostatin-like immunoreactivity in human adrenal medullae and in a pheochromocytoma is also reported. No neurotensin could be detected in the pheochromocytoma.     

Increase of substance P in primary afferent nerves during chronic pain

Substance P was found to be increased in the sciatic nerve of rats suffering chronic pain due to adjuvant-induced polyarthritis. This increase of substance P in primary afferents is assumed to reflect adaptive changes initiated by chronic noxious events such as inflammation.     

Uptake of prolactin from cerebrospinal fluid in rat brain

The fate of prolactin in the cerebrospinal fluid was studied by the use of fluorescein labelled prolactin. The distribution was compared to the immunocytochemical distribution of endogenous prolactin. High intensity fluorescence was found in the ependyma of the area postrema, rostral dorsolateral cerebral aqueduct close to the subcommissural organ, and in some cells of the floor of the cerebral aqueduct. This distribution was not seen when excess unlabelled prolactin was injected. The results suggest prolactin uptake from CSF at specific sites which correspond to sites of localization of immunoreactive prolactin.     

Co-occurrence of immunoreactive corticotrop in-like and α-melanotropin-like material in pituitary cells: Differences between young and adult rats

We examined to which extent adrenocorticotropin (ACTH)-like substances are cleavable into α-melanotropin (MSH)-like material by application of exogenous enzymes on pituitary sections prior to immunocytochemical stainings. In pro-opiomelanocortin (POMC) cells of the anterior lobe from developing rats (1 to 21 postnatal days) at least one of two cells contained α-MSH-like immunoreactivity besides ACTH-like immunostaining. Pretreatment of these tissue sections with tryptic enzymes enhanced remarkably α-MSH-like immunostaining. In contrast, α-MSH-lik immunoreactivity was almost not detectable in anterior lobes from adult rats, also after treatment with enzymes. After adrenalectomy (ax) POMC cells in anterior lobes behaved similarly: a few days after the operation almost all ACTH cells contained also α-MSH immunostaining, whereas after more than two weeks α-MSH immunostaining was nearly absent, also after application of enzymes. In contrast to rats, in young and adult guinea pig pituitaries all ACTH-like immunoreactivity was prevented by treatment with tryptic enzymes. These observations are consistent with the assumption that occurrence of ACTH- and α-MSH-like substances in rat pituitaries is regulated by a protection mechanism against proteolytic cleavage in the ACTH sequence which appears with delay in differentiating and maturing cells.     

PHI stimulates intestinal fluid secretion

Regulatory peptides are likely to have a role in the control of net intestinal fluid transport. PHI is a peptide recently isolated from porcine duodenum which has been shown to have sequence homologies with other peptides of the glucagon-secretin family. We have studied the effect of intravenous infusion of synthetic PHI on net intestinal fluid transport in the rat small intestine. During PHI infusion net absorption was reduced in the duodenum and jejunum and net secretion was observed in the ileum. Thus synthetic PHI appears to be capable of strongly stimulating intestinal secretion in the rat.     

A peptidases-resistant glycosylated analogue of substance P-(5–11). Specificity towards substance P receptors

Glycosylated analogues of the C-terminal heptapeptide of substance P either free or blocked on the N-terminal glutamine were synthesized in order to develop a metabolically stable peptide that would have an increased specificity for one type of receptor. Of the analogue described, {N-α-Boc-β-D-Glc-p (1 → 5) Gln}-Gln-Phe-Phe-Gly-Leu-Met-NH₂ is highly resistant to degradation on exposure to rat hypothalamic slices. This glycosylated peptide is about one third as potent as substance P in eliciting contractions of the guinea-pig ileum and is almost devoided of affinity for the ¹²⁵I-Bolton Hunter-SP specific binding sites on rat brain synaptosomes.     

The ribosomal synthesis and release of methionine-enkephalin and substance P by spinal cord and brain cell cultures

Peptide synthesis and release in primary dissociated nerve cell cultures have been studied using a very high specific activity, radiolabeled amino acid precursor, high-performance liquid chromatography and amino acid sequencing of purified peptides. The combined use of these methods has resulted in the rigorous demonstration of ribosomal synthesis of methionine-enkephalin by spinal cord cells, the basal release of methionine-enkephalin by spinal cord and substance P by brain cells, the tetrodotoxin sensitivity of this spontaneous release, and the potassium depolarization induced release of both peptides in a calcium dependent manner. This approach to the study of the development and biological chemistry of peptidergic neurons is recommended as a model because of the accessibility of the cells under conditions of ongoing physiologic function and the unequivocal nature of the chemical characterization of synthesized peptides.     

Differences between rats and guinea pigs in gastrointestinal and nervous system substance P levels

Substance P immunoreactivity was measured in regions of the gastrointestinal and nervous systems of age-matched adult rats and guinea pigs. Guinea pigs were found to have substantially higher substance P levels than rats in the gastrointestinal system, in dorsal roots and ganglia, and in dorsal spinal cord. Rats had higher levels in hypothalamus while levels in corpus striatum and ventral spinal cord were comparable in both species. Treatment of guinea pigs with parenteral capsaicin reduced substance P levels only in dorsal roots and ganglia and in dorsal spinal cord.     

Changes in thought content following sleep deprivation in depression

This article examines the relationship between elements of the self-concepts of depressed persons and changes in mood which are stimulated by a biological intervention (sleep deprivation). In a pilot study, seven depressed patients were tested before and after sleep deprivation to rate their thinking about their personal life issues or themes. The changes in thought content were then compared and contrasted with changes noted on the Beck, Hamilton, and POMS. As in previous studies, we found that sleep deprivation in the short-term alleviates depressed mood. While there is overall change in the direction of alleviation of depressive thought content, patients showed very individualized patterns of change in the ways they thought about their problems. These are differences in the way individual thought content changes which are not addressed by standardized tests.     

Immunoreactive substance P and somatostatin in the cerebrospinal fluid of senile parkinsonian patients

The concentration of substance-P-like immunoreactivity (SPLI) and somatostatin-like immunoreactivity (SLI) in the lumbar spinal fluid of senile parkinsonian patients (mean age 77.6 +/- 6.7 years) and senile control patients (mean age 83.5 +/- 5.6 years) were determined by specific radioimmunoassays. Mean SPLI and SLI levels in the control group were 8.1 +/- 2.0 (SD) and 32.5 +/- 12.0 fmol/ml, respectively. The mean SPLI levels were not significantly different in the groups. The mean SLI level was significantly lower in the group of patients with Parkinson's disease (19.8 +/- 9.0 fmol/ml). A comparison with results in patients with senile dementia of Alzheimer type (SDAT) shows that, in addition to clinical and pathological correlations, Parkinson's disease of late onset may share a deficit in somatostatinergic neuromodulation with SDAT.     

Changes in hippocampal immunoreactive dynorphin and neoendorphin content following intra-amygdalar kainic acid-induced seizures

Kainic acid (KA) injected focally into the amygdala induced spontaneous recurrent motor seizures. One to 6 hr after the injection of KA, the hippocampal ir-dynorphin (ir-DYN) was significantly lowered whereas 24 hr after the injection it increased. The hippocampal level of ir-alpha-neoendorphin decreased 6 hr after KA injection, and reached the control level 24 hr after the injection. Chlordiazepoxide (5 mg/kg) and phenobarbital (40 mg/kg) blocked convulsions as well as the increase in the ir-DYN content. Cycloheximide (500 micrograms icv) also antagonized the increase in the hippocampal ir-DYN. The above findings suggest that hippocampal dynorphin-related peptides are released during the seizures and that these peptides may play a physiological role in the seizure phenomena and limbic excitability.     

The effects of somatostatin, its fragments and an analog on electroconvulsive shock-induced amnesia in rats

In the present study the effects of intracerebroventricularly [icv] administered somatostatin [linear and cyclic], somatostatin3-6, somatostatin7-10 and des AA1,2,4,5,12,13 [D-Trp8] somatostatin [ODT8-SS] were investigated on electroconvulsive shock [ECS]-induced retrograde amnesia in rats. The ECS significantly decreased the foot shock-induced avoidance latency, and thus caused retrograde amnesia. Somatostatin [linear and cyclic] in a dose of 0.6 nM had no action on the ECS-induced retrograde amnesia, while in doses of 3 nM and [cyclic only] 6 nM it significantly prevented it. Somatostatin3-6, somatostatin7-10 and ODT8-SS in doses of 0.6, 3 and 6 nM had no effect on the ECS-induced amnesia. These results indicate that the whole sequence of the original somatostatin molecule is needed to block the ECS-caused retrograde amnesia.     

Cardio-respiratory actions of substance P, TRH and 5-HT in the nucleus tractus solitarius of rats: evidence for functional interactions of neuropeptides and amine neurotransmitters

The cardiovascular and respiratory effects of Substance P (SP) and Thyrotrophin-Releasing Hormone (TRH) microinjections into the nucleus tractus solitarius (NTS) of urethane anaesthetized rats have been investigated. Dual injections of the peptides with serotonin (5-HT) were given to investigate possible functional interactions. In addition, SP and TRH were injected into rats in which 5-HT in the NTS area had been depleted by prior treatment with 5,7-Dihydroxytryptamine (5,7-DHT). SP (65pmol) did not elicit significant effects on blood pressure (BP) or heart rate (HR), but produced a marked, acute reduction in respiration rate (RR). TRH (110pmol) elicited a small but significant reduction in mean arterial pressure (MAP), whereas 5-HT (15nmol) caused a rise in MAP. Neither TRH nor 5-HT modified RR when given alone. A dual injection of SP (6.5pmol, ineffective alone) and 5-HT (15nmol) resulted in a rise in MAP which was insignificantly different from the effect of 5-HT alone. However, a prolonged fall in RR, unlike the effect of SP alone was also observed. A dual injection of TRH (11pmol, ineffective alone) and 5-HT (15nmol) resulted in a profound fall of RR but no significant changes in MAP or HR. SP elicited similar effects in 5,7-DHT lesioned animals as in sham operated controls. In contrast, TRH microinjections in lesioned rats were associated with a profound fall in RR, and a blood pressure response significantly different to that observed in the corresponding sham group. The results are discussed in relation to other evidence suggesting functional interactions between neuropeptides and amine neurotransmitters in the mammalian brainstem.     

Enkephalin-like immunoreactivity in Drosophila melanogaster

Enkephalin-immunoreactive neurons have been identified in the central nervous system of the fruit fly Drosophila melanogaster by immunocytochemical techniques. Analyses of fly extracts by high performance liquid chromatography and radioimmunoassay show a relatively complex pattern of immunoreactive compounds. The most prominent among them has chromatographic properties similar to those of met-enkephalin from which can, however, be distinguished by high-resolution chromatographic techniques.     

Stria terminalis axons ending on substance P and neurotensin-containing cells of rat central amygdaloid nucleus: An electron microscopic immunocytochemical study

Immunocytochemistry at the electronmicroscopic level was used to identify and examine substance P and neurotensin-containing perikarya and dendrites in the central amygdaloid nucleus of the rat. Following unilateral transection of the stria terminalis between the bed nucleus of the stria terminalis and the amygdala, degenerated nerve terminals were present in the ipsilateral central amygdaloid nucleus. These degenerated boutons were associated with both perikarya and dendrites of substance P and neurotensin-positive cells as well as unlabeled neurons.     

Ipsiversive rotation elicited by electrical stimulation of the mesencephalon in the rat: Anatomical,physiological, and pharmacological considerations

Electrical stimulation at a variety of sites in the ventral mesenecphalic reticular formation of rats produced stimulus-bound rotation toward the side being stimulated. The effective sites occupied a clearly circumscribed area well posterior to the hypothalamic sites that have been reported to produce contraversive rotation. In a number of cases other motor phenomena such as limb movements or tremor were also observed, but these always involved the side of the body contralateral to that being stimulated. The anatomical distribution of the sites producing ipsiversive rotation along with the fact that rotation was only partially blocked by haloperidol suggest the existence of a major noncatecholaminergic rotation system that operates in a manner antagonistic to and independent of the nigrostriatal dopamine system.     

beta-lipotropin increases ketone body plasma concentration in rabbits

beta-lipotropin stimulates lipolysis in the rabbit in a dose dependent manner. Besides glycerol and free fatty acid release a significant increase of betahydroxybutyrate as well as of acetoacetate was observed while pyruvate decreased significantly. Glucose and lactate levels remained unchanged. Our data suggest that lipolysis induced by beta-LPH and its effect on ketogenesis is more important than the actual plasma concentration of insulin.     

Visual properties of neurons in the posterior suprasylvian gyrus of the cat

Morphine sulfate exerts its analgesic action in part through suppression of the activity of spinal cord nociceptive neurons. Cells in Rexed lamina VII are considered to be the cells of origin of the spinothalamic and spinoreticular tracts concerned with nociception. Using graded radiant heat to their peripheral receptive fields, the relationship between the intensity of heat (millicalories per square centimeter per second) which produces noxious stimuli and the response frequency of single units in Rexed lamina VII of the spinal cord was analyzed with extracellular microelectrode recording techniques in 15 decerebrated and spinal-transected cats before and after administration of morphine sulfate (1 mg/kg, iv). A linear relationship between the intensity of heat and the frequency of response discharge was observed (above threshold) both in the control study and after the administration of morphine. Morphine sulfate significantly suppressed the spontaneous activity of the units studied, raised the threshold of their evoked activity to varying intensities of heat, and diminished the slope of the heat intensity vs evoked single-unit response relationship. Naloxone (0.02 mg/kg, iv) eliminated all changes brought about by morphine sulfate.