Somatostatin: Interaction with the sympathetic nervous system in guinea pigs

We have investigated the cardiovascular effects of somatostatin (SS) in anesthetized guinea pigs. SS was found to produce a dose-dependent vasodepressor effect and bradycardia. The size of the vasodepressor response to SS was dependent on the pre-injection level of blood pressure. The higher the blood pressure was, the larger was the response to SS. Atropine (1 mg kg^?1) did not alter the effects of SS thus suggesting that SS neither activates cholinergic nerves nor interacts with muscarinic receptors. SS (5 μg kg^?1 min^?1) markedly inhibited the pressor effects of dimethylphenylpiperazinium (DMPP), a relatively specific ganglionic stimulant, and of isoproterenol, a beta receptor agonist, without interfering with their positive chronotropic effects. The pressor effects and tachycardia evoked by bolus injections of noradrenaline and of tyramine were usually enhanced during SS infusions. Guanethidine, a drug known to paralyse adrenergic neurons, modified similarly to SS, the cardiovascular effects of noradrenaline and of DMPP. The results suggest that the vasodepressor effect of SS results from a selective depression of the sympathetic outflow to the blood vessels via a presynaptic inhibitory effect on adrenergic neurons. The slowing of heart rate caused by SS is most likely the result of a direct depressant effect on the sinoatrial node.     

Evidence from thymidine labeling for continuing growth of retina and tectum in juvenile goldfish

Chronic temporal lobe seizures were induced in 11 monkeys by bilateral implantation of aluminum hydroxide into the hippocampi. With unilateral temporal lobe implants of alumina little or no epileptic activity was found; however, with bilateral alumina implants clinical seizures similar to human psychomotor attacks were initiated in either of the affected temporal lobes. Spread of alumina through the ventricles and/or tissue in some animals resulted in other seizure types, most of which could be controlled by phenobarbital, without eliminating the temporal lobe seizures. The alumina temporal lobe seizures recurred spontaneously for indefinitely long periods; however, no monkey was studied longer than 14 months. The onset of seizure activity was followed by transient anorexia and adipsia which, with large alumina volumes or other debilitating factors, could progress to fatal status epilepticus. Histology revealed that tissue reactions to the alumina included cell loss, gliosis, and neovascularization, with the most severe reaction occurring adjacent to the alumina mass. Alumina which had leaked into the ventricles in some animals reentered the brain tissue at remote sites through the choroid plexus, resulting in multiple foci.     

Effects of unilateral spinal cordotomy and outer ear occlusion on audiogenic seizures in mice.

After cortical superfusion with taurine, an electroencephalographic and biochemical study was performed in cats affected with unilateral and bilateral penicillin epileptogenic foci. Taurine-treated cats showed a depressed epileptic susceptibility of the cortex, which was more remarkable in the less severe epileptic picture produced by unilateral penicillin. Both in control and in epileptogenic cortex, at the end of taurine superfusion, the amino acid content in brain was altered only for taurine and glutamic acid, which were increased and decreased, respectively. The subsequent changes in the brain concentration of these two compounds were the opposite, i.e., taurine decreased and glutamate increased, and a significant negative correlation between the cortical concentrations of the two amino acids was calculated. The rapidity of the changes was greater in epileptogenic than in control cortex, and maximal in the severe epilepsy produced by bilateral penicillin. Furthermore, the rapidity of the changes decreased during and after the disappearance of spikes. The hypothesis is put forward that the changes in brain content of taurine and glutamate observed after taurine cortical loading share the responsibility for the depressed epileptic susceptibility of the cortex. The common enzyme involved in the metabolism of taurine and glutamate could be responsible for the negative correlation between the two compounds.     

Ontogeny of cortical and subcortical electroencephalographic events in unrestrained neonatal and infant rats

We have devised a method of stereotaxic implantation of electrodes in cortical and subcortical sites in neonatal and infant rats and subsequently recording from these animals as they move about freely. We studied the development of the EEG recorded from these cortical and subcortical sites in animals ranging in age from 1 to 84 days and analyzed the EEGs both visually and by power spectral analysis via a fast Fourier transform algorithm. The animals survived the procedure with less than 5% overall mortality. Although of very low voltage and very irregular in appearance, EEG activity was present in all sites at 1 day of age. There was gradual increase in synchrony, organization, and voltage until 12 to 14 days when an adult pattern appeared.     

Altered responsiveness of adenosine 3′,5′-monophosphate-generating systems in brain slices from adult rats after neonatal treatment with 6-hydroxydopamine

Sprague-Dawley rat pups were administered 6-hydroxydopamine (100 mg/kg) subcutaneously on each of the first 4 days after birth. At 4–5 mo of age the rats and untreated littermates were killed, and the accumulation of [¹⁴C]cyclic AMP elicited by various agents in [¹⁴C]adenine-labeled brain slices was investigated. The accumulation of cyclic AMP elicited by norepinephrine was significantly greater in slices from neocortex and midbrain of 6-hydroxydopamine-treated rats than in corresponding slices from littermate controls. Accumulations in slices from medulla-pons and cerebellum were not significantly altered by the neonatal treatment with 6-hydroxydopamine. Thus, an enhanced response to norepinephrine pertains both in a region, the neocortex, where norepinephrine-levels were permanently reduced by neonatal treatment with 6-hydroxydopamine and in a region, the midbrain, where adult levels of norepinephrine were nearly doubled by the neonatal treatment with 6-hydroxydopamine. Enhanced responses of cyclic AMP-generating systems in neocortical slices from 6-hydroxydopamine-treated rats also pertained with isoproterenol, prostaglandin E₁ and an adenosine-norepinephrine combination, but not with adenosine alone. Depletion of norepinephrine throughout the brain by administration of either reserpine or intraventricular 6-hydroxydopamine to adult rats enhanced responses to norepinephrine in slices from neocortex, but not midbrain. Reserpine had no effect on responses in either neocortex or midbrain of rats treated neonatally with 6-hydroxydopamine.     

Influence of nerve cell body and neurolemma cell on local axonal protein synthesis following neurotomy

The influence of the nerve cell body and neurolemma cell on selected aspects of local axonal protein synthesis as a consequence of neurotomy was studied in the hypoglossal nerve. The onset of the phase of rapid local protein synthesis in axons of the proximal stump, occurring 12–15 hr after transection, was not affected by decentralization at the time of neurotomy. This indicated that the perikaryon was not required to induce the rapid local synthesis response. Moreover, other experiments demonstrated that this response could be induced in intact nerve in regions subjected to gentle blunt dissection of the nerve away from surrounding tissue. Incorporation of [³H] leucine into axonal protein in proximal stumps, 18 hr after transection, occurred without apparent delay and proceeded at a linear rate through 2 hr in vitro. In addition, incubation in vitro with colchicine produced no significant effect on local synthesis of axonal protein. These findings were consistent with an intra-axonal site of protein synthesis and a local induction of the phase of rapid axonal protein synthesis.     

Intracameral administration of alpha-MSH increases intraocular pressure in rabbits

A growing body of evidence suggests that neural peptides may induce important modulations on vegative and motor functions of the eye. The present study was designed to evaluate the effect of intracameral (I.C.) administration of alpha-melanocyte-stimulating hormone (alpha-MSH) and several other ocular peptides on intraocular pressure (IOP) in rabbits. alpha-MSH (5 micrograms) produced a significant and prolonged unilateral increase of IOP. This effect of I.C. alpha-MSH was dose-dependent (ED50 = 2.5 micrograms). Structure-activity studies revealed that equimolar doses of beta-MSH and gamma-MSH, unlike alpha-MSH, were totally ineffective. In addition, the structurally unrelated peptides beta-endorphin, thyrotropin-releasing hormone (TRH) and gonadotropin-releasing hormone (Gn-RH) did not affect IOP, when tested in a dose equimolar to 5 micrograms of alpha-MSH. These results confirm and extend previous observations, suggesting that alpha-MSH may be an important factor involved in regulation of IOP.     

Degradation of basic protein and Wolfgram protein in central nervous system by soluble enzymes of human peripheral polymorphonuclear leucocytes

The present communication describes the ability of soluble enzymes (SE) of peripheral polymorphonuclear leucocytes of control and multiple sclerosis (MS) patients to degrade major myelin proteins of MS and control myelin. MS and control SE degraded in situ both Wolfgram protein (WP) and basic protein (BP) of isolated myelin. No differences were found between the action of control and MS patients SE on myelin. However, significantly less degradation of BP and WP in control myelin compared to that in MS myelin was found. Only 30% of SE samples (both control and MS) degraded significant amounts of proteolipid protein in myelin. It is postulated that SE associated demyelination in MS may be a factor contributing to the demyelinating process.     

Cholecystokinin in the central nervous system: A minireview

This review focuses on the structure, distribution, neuronal pathways, receptor binding, release, biosynthesis and degradation of CCK in the central nervous system. Other aspects of the isolation and chemistry of CCK (1), its role in satiety (2), as a hormone or neurotransmitter (3,4), and its evolution (5) have been reviewed recently.     

Brain stem projections to lobule VII of the posterior vermis in the squirrel monkey: as demonstrated by the retrograde axonal transport of tritiated horseradish peroxidase.

In streptozotocin-diabetic female rats acute (24 h) withdrawal of insulin significantly impairs both estradiol+progesterone-induced sexual receptivity and cell nuclear concentration of [³H]estradiol in hypothalamus, preoptic area, and pituitary gland. Omission of insulin treatment for the first 24 h of a 30-h or 54-h estradiol benzoate-conditioning period significantly reduced mean lordosis ratings of ovariectomized-diabetic rats. Insulin withdrawal at the time of progesterone treatment and behavioral testing did not diminish sexual receptivity. One-half or 2 h after an intravenous injection of [³H]estradiol-17β diabetic rats without insulin exhibited reduced cell nuclear [³H]estradiol concentrations (2 h) and/or diminished cell nuclear/whole homogenate concentration ratios (0.5 and 2 h). Twenty-four hour insulin withdrawal affected neither whole tissue [³H]estradiol uptake nor hypothalamus-preoptic area cytoplasmic estrogen-receptor content. These results: (1) suggest that diminished estradiol binding by target tissue cell nuclei may contribute to the well-known reproductive failures of female diabetics, and (2) support the concept that estradiol acts at the level of brain cell nuclei to induce female sexual behavior.     

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.     

Effects of nerve growth factor administration of N-ethyl-N-nitrosourea carcinogenesis.

We attempted to determine whether the sympathetic nervous system in rodents is susceptible to co-carcinogenesis, employing murine salivary nerve growth factor (NGF) as a co-carcinogenic agent. NGF had no co-carcinogenic effect with either methylcholanthrene or ethylnitrosourea (ENU) on the sympathetic nervous system of the mouse, whether administered transplacentally, postnatally, or both transplacentally and postnatally. At a dose of ENU of 30 mug/g body weight, NGF did not shorten the latent period for tumor induction of BD-IX rats. In contrast, a 25% reduction in latent period was brough about by NGF for tumor appearance in BD-IX rats receiving 90 mug/g ENU. In both cases the frequency of urogenital tumors in rats was increased as a result of NGF administration, at the apparent expense of neural tumors.     

Induction of disseminated intravascular coagulation by endotoxin and saline loading in rats I. The influence on fibrinogen turnover and plasma parameters

In rats a single injection of 1 mg endotoxin and a subsequent infusion of normal saline induced a disseminated intravascular coagulation. A nearly complete defibrination and a decrease of platelets coincided with high amounts of plasma hemoglobin and fibrin/fibrinogen degradation products. Fibrinogen kinetics were investigated by use of 131-I-fibrinogen. The biological half life was 24.1 hours corresponding to a catabolic rate of 78 mg/24h/kg b.w. After triggering the intravascular coagulation the turnover of 131-I-fibrinogen revealed three phases: 1. “acute phase” with a catabolic rate of approx. 780 mg/24h/kg b.w., 2. “subacute phase” with a catabolic rate of 274 mg/24h/kg b.w. and 3. “repair phase” with a catabolic rate approximating to normal values. During the “subacute phase” the fibrinogen level increased above normal, demonstrating that in spite of an increased fibrinogen catabolism due to DIC elevated plasma fibrinogen levels can be found.     

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.     

Neuronal activity of the locus ceruleus in awake Macaca arctoides

Neuronal activity in the locus ceruleus of awake, behaving stump-tailed monkeys increased consistently and vigorously after presentation of mildly aversive and threatening stimuli. These preliminary data increase the range of stimuli reported to elicit locus ceruleus activity in awake monkeys to include nonpainful threat signals and suggest that more studies are needed to be able to categorize locus ceruleus function from its unit activity responses.     

Stimulation and maintenance by nerve growth factor of phenylethanolamine-N-methyltransferase in superior cervical ganglia of adult rats

Treatment of newborn rats with nerve growth factor (NGF) results in a striking increase in phenylethanolamine-N-methyltransferase (PNMT) in the superior cervical ganglia. Between one and three weeks of age there is normally a 10-fold decrease in PNMT activity in ganglia of infant rats. NGF treatment maintains the PNMT in ganglia at levels 10-fold greater than in untreated controls, but the levels of enzyme in the ganglion show the same magnitude of decrease with age. Epinephrine levels are markedly increased in ganglia of NGF-treated rats younger than one week of age, but at older ages the levels of the catecholamine are only slightly greater than the controls. Dexamethasone is less effective than NGF in increasing the levels of PNMT in ganglia of infant rats and, unlike NGF, becomes ineffective by 44 days of age. These results suggest that there may be two types of PNMT-containing cells in ganglia of newborn rats.     

Changes in the concentration of somatostatin and substance P in the cerebrospinal fluid following injection of alcohol into the pituitary gland

The concentration of immunoreactive somatostatin and Substance P in the cisternal cerebrospinal fluid (CSF) of patients with pain due to malignant disease has been measured before and after injection of alcohol into the pituitary fossa. Following the first injection, a rise of 108 +/- 66% in CSF somatostatin levels was observed in 7 out of 13 patients, and a rise of 87 +/- 26% in 4 out of the 5 patients undergoing a second injection. A rise of 179 +/- 99% in levels of Substance P in CSF was observed in 4 out of 8 patients after a single injection. No change in peptide concentration was detected in peripheral plasma. Changes in CSF levels did not correlate with the degree of pain relief obtained, but patients with the greatest increase in somatostatin subsequently developed diabetes insipidus. The data are consistent with our previous experience that injection of alcohol into the pituitary fossa can cause destruction to nervous tissue, in addition to the obvious destruction of pituitary gland tissue. They do not support the suggestion that hypothalamic damage is necessary in order to obtain pain relief.     

Primary afferent depolarization evoked by electroacupuncture in the lumbar cord of the cat

In precollicular decerebrate cats, experiments were performed to ascertain the presence of primary afferent depolarization at the slowly conducting fiber terminals of the sural nerve, in an attempt to substantiate our previous postulation of a possible presynaptic mechanism underlying acupuncture analgesia in the spinal cord. A well correlated temporal course has been observed to exist between the negativity of dorsal root potential, suppression of sural polysynaptic reflexes, and increased excitability of sural primary afferent terminals, under the influence of the same electroacupuncture to the left tsusanli point in the hindlimb. Furthermore, by a collision test and conduction velocity measurement, the acupuncture-evoked primary afferent depolarization thus indicated was found to occur solely at the terminals of the slowly conducting fibers of the sural nerve, fibers believed to transmit “pain” impulses. As primary afferent depolarization has powerful inhibitory actions and its existence is well demonstrated in the spinal cord and trigeminal system, we suggest that acupuncture can also utilize this well established mechanism in modulating “pain” information at the primary afferent level in the spinal cord. This spinal presynaptic inhibitory mechanism, however, is thought to be only a part of an overall process underlying the production of acupuncture analgesia.     

Recurrent peripheral nerve palsies and concomitant chronic neuropathy. Neuromusclar electrophysiologic study and neuropathologic examination: apropos of 5 cases]

The authors report 5 personal cases (3 in the same family) of patients suffering from recurrent peripheral nerve palsies usually induced by pressure and review the relevant literature. There is evidence in such cases of a mild, chronic, diffuse, subclinical neuropathy which can be recognized by electrophysiological examination. Examination of peripheral nerve biopsy material in such cases shows evidence of both axonal and Schwann cell abnormalities with evidence of neurogenic atrophy of skeletal muscles. This chronic subclinical neuropathy which is often familial can be distinguished from other chronic primary neuropathies with or without myelin sheath proliferation and hypertrophy.