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PubMed1985

Specific binding of [3H]substance P to the rat submaxillary gland. The effects of ions and guanine nucleotides.

[3H]Substance P ([3H]SP), in a high ionic strength incubation medium, binds to a single class of saturable, noninteracting binding sites on rat submaxillary gland membranes with a KD = 2.8 +/- 0.34 nM and maximum binding (Bmax) = 220 +/- 31 fmol/mg of protein. The rank order of potency of various tachykinins, SP fragments and analogs to compete against [3H]SP is correlated with their potency to induce salivation. These findings indicate that, under the conditions described, [3H]SP binds to a physiologically relevant tachykinin receptor of the SP-P subtype. [3H]SP binding increases by 35% in the presence of optimal concentrations of Mn++ and Mg++ whereas guanine nucleotides reduce [3H]SP binding. The effect produced by either divalent cations or guanine nucleotides is due to increasing or decreasing the Bmax, respectively, without changing the affinity of [3H]SP. Guanine nucleotides reduce the Bmax of [3H]SP to the same level in the presence or absence of divalent cations, indicating that divalent cations increase the population of SP receptors that are sensitive to guanine nucleotides. In low ionic strength media, and when the nonspecific binding is defined by 1 microM SP, [3H]SP binds to two sites: a high affinity site with a KD of 0.14 nM and a Bmax of 370 fmol/mg of protein and a low affinity high capacity site. When the nonspecific binding is defined by 1 microM physalaemin, the high affinity is the only detectable site. However, in low ionic strength media, physalaemin has about one-fiftieth the potency of SP in competing with [3H]SP. These results prove that increasing the ionic strength of the media reduces the affinity of SP and some of its fragments and allows the determination of physiologically relevant SP-P binding sites.

Animals↗
PubMed1986

Conformationally constrained tachykinin analogs which are selective ligands for the eledoisin binding site.

We have prepared a series of conformationally constrained hexapeptide analogs of substance P which are 500-1500-fold more potent as inhibitors of 125I-labeled Bolton Hunter-conjugated eledoisin binding to rat brain cortex membranes than as inhibitors of 125I-labeled Bolton Hunter-conjugated substance P binding. These analogs stimulate guinea pig ileum contraction (ED50 1-16 nM) and stimulate rat vas deferens contraction (ED50 2-4 microM). However, these peptides are poor stimulators of rat salivation (greater than 40 nmol/100 g body weight). Thus, based on both their receptor potency and pharmacological potency, these peptides are potent and selective tachykinin analogs. These data indicate that a specific carboxyl-terminal conformation is recognized by the 125I-labeled Bolton Hunter-conjugated eledoisin binding site and that this conformation is different from the conformation recognized by the 125I-labeled Bolton Hunter-conjugated substance P binding site. Hexapeptides containing phenylalanine, isoleucine, and valine identical with the carboxyl-terminal sequences of substance P, eledoisin, and neurokinin B, respectively, were nearly equipotent as inhibitors of 125I-labeled Bolton Hunter-conjugated eledoisin binding. The valine analog was only approximately 5-fold less potent than the isoleucine and phenylalanine analogs as an inhibitor of 125I-labeled Bolton Hunter-conjugated substance P binding. Thus, unknown determinants in the amino-terminal sequences of substance P must strongly contribute to the carboxyl-terminal peptide selectivity and conformation. The contraction of guinea pig ileum induced by one of the conformationally constrained analogs is attenuated by pretreatment of the tissue with atropine (2 microM), while that induced by substance P methyl ester, a selective inhibitor of 125I-labeled Bolton Hunter-conjugated substance P binding, is not. Thus, the constrained analog has a higher affinity for the tachykinin receptors in the guinea pig myenteric plexus which are responsible for acetylcholine release than for the tachykinin receptors present on the smooth muscle cells.

Acetylcholine↗
PubMed1987

Interaction of hexachlorocyclohexane and malathion in male guinea pigs after repeated dermal application.

Repeated application of hexachlorocyclohexane (HCH; 50 and 100 mg/kg) and malathion (200 and 400 mg/kg) alone or in combination daily for 30 days on the skin of male guinea pigs caused mild to severe signs of toxicity and death of animals. The experimental animals exhibited tremor, dyspnea, salivation, convulsion, diarrhea and paralysis of the limbs. These were associated with significant biochemical and morphological changes in skin, liver, kidney and testes. The inhibition of acetylcholinesterase appeared highly significant in the combined treatment, but was not suggestive of any HCH and malathion potentiation. The highest level of HCH residue was seen in fatty tissue after low dose treatment. This was in contrast to the high level seen in liver after larger doses of HCH. This study suggests that HCH and malathion did not elicit any potentiation effects in the parameters monitored and at the doses tested.

Acetylcholinesterase↗
PubMed1987

Toxicosis in newborn pigs associated with cutaneous application of an aerosol spray containing chlorpyrifos.

Weakness, lethargy, ataxia, lateral recumbency, limb paddling, tremors, salivation, and diarrhea were observed in newborn pigs on a commercial swine farm. Many pigs became moribund and died. All had been treated with an aerosol wound spray containing 2.5% chlorpyrifos. A controlled study was undertaken to determine whether the aerosol spray was the cause of these clinical signs. Pigs exposed to aerosol spray containing 2.5% chlorpyrifos at 3 hours (n = 4) and 6 hours (n = 3) after birth developed clinical signs similar to those on the farm; none survived. Pigs exposed at 24 hours (n = 5) after birth developed clinical signs consistent with those that had developed in pigs on the farm; 3 died and 2 survived. Of 3 pigs exposed to the same spray at 36 hours after birth, 1 developed tremors 7.5 hours later and diarrhea 9 hours later, then returned to normal.

Aerosols↗
PubMedDate not supplied

[Ultrastructure of the submandibular glands in rats kept in weightlessness].

Submandibular salivary glands of male rats weighing 330-350 g were examined after space flight and ground-based control study. Light microscopy was carried out using hematoxylin-eosin staining and PAS-reaction. Electron microscopy was performed using glutaraldehyde and osmium tetroxide fixation and contrasting according to Reynolds. Light microscopy revealed no destructive changes in the gland parenchyma; differences between flight and control rats remained within physiological limits. Electron microscopy of acinar cells of flight animals showed chromatin condensation, darkening of cells and nuclei, appearance of electron-dense vacuoles, fragmentation fo the granular endoplasmatic reticulum as well as enlargement of interstitial spaces, lumens of acini and intercellular canaliculi, loosening of basal membranes, and thinning of capillary walls. Electron microscopy of acinar cells of control rats demonstrated chromatin condensation in nuclei and fragmentation of the GER. Thus, both animal groups exhibited ultrastructural signs of inhibition of the synthesis and excretion of salivary protein. In addition, flight animals showed increased excretion and, probably, secretion of water and electrolytes. Examinations of granulocytes revealed enlargement of secretory granules in both animal groups, the largest granules being seen in flight animals. They also showed mitochondrial swelling which was most significant in control rats. After the ground-based study cells of the striated compartment also displayed a very distinct mitochondrial swelling which may reduce the reabsorption capacity and enhance salivation of the compartment. However the mechanism of these changes seems to be different from that underlying changes after real space flight.

Animals↗
PubMed1988

Comparison of histamine release induced by morphine and oxymorphone administration in dogs.

Cardiovascular effects (vasodilatation, hypotension) of morphine administration have been attributed to central actions and peripheral histamine release. In the study reported here, we compared plasma histamine (Hm) concentrations after morphine sulfate and oxymorphone HCl administration in conscious dogs. Five healthy adult dogs (mean body weight, 10.1 kg) were randomly administered morphine (2 mg/kg of body weight, IV) or oxymorphone (0.2 mg/kg, IV) by a 5-second bolus injection at weekly intervals. Venous blood samples (5 ml) were collected from jugular veins before and at 1, 2, 5, 15, 30, and 60 minutes after drug administration. Behavioral changes were recorded. Plasma was analyzed by a radioenzymatic technique, using purified histamine N-methyltransferase as an enzyme catalyst (sensitivity of assay, 40 pg Hm/ml). Mean base-line Hm value for all dogs was 0.55 ng/ml. The mean Hm value was significantly higher (P less than 0.05) than the base-line value at 1, 2, 5, 15, and 60 minutes after morphine administration (531.4, 251.0, 113.0, 31.5, and 1.0 ng of Hm/ml, respectively), but there were no significant increases in histamine values from base-line values at any time after oxymorphone administration. All dogs given morphine and 1 dog given oxymorphone showed excitatory behavior; 2 dogs given morphine and 3 dogs given oxymorphone salivated profusely.

Animals↗
PubMed1989

Discriminative stimulus effects of naltrexone in morphine-treated rhesus monkeys.

Three adult, female rhesus monkeys responded under a fixed-ratio 5 schedule of stimulus-shock termination while discriminating between s.c. injections of saline and naltrexone (0.01 mg/kg). In addition, monkeys received daily injections of morphine (1.78 or 3.2 mg/kg) 3 hr before experimental sessions. With increasing doses of naltrexone monkeys switched in a dose-related manner from the saline to the naltrexone lever; complete generalization (greater than 80% responding on the naltrexone lever) occurred in all monkeys at doses of naltrexone larger than 0.0032 mg/kg. Doses of naltrexone that produced responding on the drug lever also produced effects typically observed during opioid withdrawal (e.g., miosis and salivation). Compounds with opioid mu antagonist effects under other conditions (e.g., nalorphine) substituted for naltrexone whereas a wide variety of opioid agonists (e.g., morphine, U-50,488 and butorphanol) as well as nonopioids (e.g., pentobarbital and ketamine) produced responding predominantly on the saline lever. Monkeys also switched to the naltrexone lever in a time-related manner after the daily injection of morphine with complete generalization occurring between 8 and 27 hr after morphine. Among a variety of opioid and nonopioid compounds, including drugs used in the treatment of opioid abuse (e.g., clonidine), only compounds with mu agonist actions under other conditions produced a switch in responding from the naltrexone to the saline lever in 27-hr morphine-abstinent monkeys. These results suggest single, daily injections of morphine are sufficient to produce dependence in rhesus monkeys and indicate further drug discrimination studies in morphine-treated rhesus monkeys might be pharmacologically more specific than observational procedures.

Animals↗
PubMed1985

Specific binding of [3H-Tyr8]physalaemin to rat submaxillary gland substance P receptor.

[3H]Physalaemin [( 3H]PHY) binds to a single class of noninteracting sites on rat submaxillary gland membranes suspended in high ionic strength media with a KD of 2.7 nM, a Bmax of 240 fmol/mg of protein, and low nonspecific binding. The relative potencies of substance P (SP) and its fragments in competing with [3H]PHY correlate with their relative salivation potencies. This indicates that [3H]PHY interacts with a physiologically relevant SP receptor. In low ionic strength media, the KD of [3H]PHY does not change, but SP and some of its fragments are more potent than PHY in competing with [3H] PHY. Computer-assisted analysis of [3H]PHY and [3H]SP binding in high and low ionic strength media demonstrated that both peptides are equipotent in high ionic strength but that the affinity of SP increases by 70-fold in low ionic strength. The SP fragments that contain a basic residue in positions 1 and/or 3 also display an increased affinity in low ionic strength. These findings document that [3H]PHY binding in high ionic strength (mu = 0.6) accurately reflects the pharmacological potencies of agonists on the SP-P receptor. The binding of [3H]PHY, like that of [3H]SP, increases by the addition of divalent cations (Mg2+ greater than Ca2+ greater than Mn2+). Guanine nucleotides decrease [3H]PHY binding by decreasing the Bmax to the same level (160 fmol/mg of protein), in the presence or absence of Mg2+.

Animals↗
PubMed1989

[Quantitative studies on the secretory output of the palatine salivary glands].

A method for the direct measurement of the secretory output of the palatine glands is described and its clinical reliability is verified in a study on 134 persons. The results showed that, if the measuring conditions are fulfilled and the measuring parameters are kept constant, the error remains below 15%. Situative influences, such as the time of the day, the date of the measurement, etc. are just of secondary importance for the measured results. The physiological secretory output of the palatine glands averages 1.36 microliters/mm2 mucosal surface, which is about 30 times as much as the values measured in patients with symptoms of hyposalivation. Personal characteristics of the persons tested such as age, sex, etc. have no major influence on the secretory output. Serial measurements during treatment with ptyalagogues supported the evidence that this measuring method is a valuable instrument in the diagnosis of salivation disorders.

Humans↗
PubMed1989

Transdermal scopolamine: a review of its effects upon motion sickness, psychological performance, and physiological functioning.

Scopolamine is the most effective single drug for the prophylaxis and treatment of motion sickness. However, oral or injected scopolamine displays a comparatively short duration of action (5-6 hours), and leads to deleterious side effects on autonomic and central nervous system cholinergic functions. The transdermal scopolamine system was designed to reduce these problems, but while it does deliver scopolamine over a prolonged time period (72 h), deleterious side effects are also produced. Transdermal scopolamine provides significant motion sickness protection, similar in extent to that provided by oral scopolamine or dimenhydrinate. Its autonomic nervous system effects comprise reduced salivation, bradycardia, and blurred vision due to reduced visual accommodation. The visual problems increase following repeated patch applications, with hypermetropic ("long sighted") individuals particularly at risk. Central nervous system effects comprise reduced memory for new information, impaired attention, and lowered feelings of alertness. Variation in response to transdermal scopolamine has also been reported, both between individuals, and between different patch applications on the same individual.

Accommodation, Ocular↗
PubMed1989

[Taste].

Taste has a dual role. Like other senses it informs the individual about the external world, but unlike other senses it connects that perception with information about the internal environment. The principal function of taste is similar in all higher species. Molecules act on specialized sensory cells (= taste cells) in various regions of the oral cavity thus triggering signals, which are relayed to the cortex via afferent nerves, the caudal hindbrain and the thalamus. Taste afferents also reach the hypothalamus and the limbic system. The taste of food triggers physiological and behavioral reactions in man and animals. Stimulation of taste cells immediately elicits salivation, secretion of gastric acid and pancreatic juice as well as secretion of gastrointestinal and pancreatic hormones. Innate and learned taste preferences or aversions play an important role in food selection and taste aversions are considered to be reliable indicators of malaise. Neural signals from the periphery or humoral factors which are sensed by receptors in the central nervous system both can change the acceptance of a certain taste. Endogenous opiates in the brain seem to play a special role in the modulation of taste perception. The amygdala is apparently a brain area which is particularly important for taste perception.

Animals↗
PubMed1977

[Etiology and pathogenesis of neurological symptoms in low bite].

50 patients were subjected to complex examination. In bite lowering the head of the condyle is displaced backwards and upwards into the depth of the glenoid fossa. The pressure of the displaced mandibular joints upon the arterial cord and the tympanic vein as well as upon the venous network around the mandibular joint capsule may produce disturbed blood supply to the mucosa of the middle ear and of the auditory tube, and finally, obstruction of the auditory tube. Disturbances in the blood supply of the middle ear irritate the tympanic cord and tympanic plexus, which causes burning of the tongue, taste and salivation troubles, and also ear complaints. Since the sympathetic fibres of the tympanic plexus and of the eye are closely interrelated, this leads also to an irritation of the dilator muscle of the pupil. The reflectory irradiations from the tympanic plexus and mandibular joint explain many other neurologic symptoms. In bite lowering these symptoms are not always associated with joint disturbances.

Adult↗
PubMed1989

[Traumatic laceration of facial nerve and Stenone duct. A clinical case].

After a brief review of the main operating techniques employed in the reconstruction of the facial nerve and Stenone's duct lacerated by trauma, a clinical case in which the two lesions are associated is reported. Suture of the lacerated nervous branches and attachment of the salivary fistula to the oral mucosa using a silicon drainage applied for a few days permitted functional recovery of neuronal activity and salivation.

Adolescent↗
PubMed1989

Zinc-induced hemolytic anemia caused by ingestion of pennies by a pup.

A 4-month-old Pomeranian pup was examined because of anorexia, salivation, and persistent vomiting. Initial laboratory testing revealed marked hemolytic anemia with spherocytosis. Survey abdominal radiography revealed 4 metal objects which, when removed by gastrotomy, were identified as pennies. Of 4 pennies, 3 were minted since 1983 and were heavily pitted over the surface and rim. Partially digested pennies were composed of a copper-plated high zinc concentration alloy. Further laboratory testing indicated a marked increase in serum zinc concentration in the pup (28.8 mg/L), confirming metal toxicosis. Serum zinc concentrations decreased during recovery.

Anemia, Hemolytic↗
PubMed1987

Pathogenesis of ovine pseudorabies (Aujeszky's disease) following intratracheal inoculation.

Pseudorabies virus was inoculated intratracheally into sheep to investigate the pathogenesis of pseudorabies virus infection. Clinical signs of pyrexia, depression, frequent swallowing, facial fasciculations, chorea, excessive salivation, mild tympanites, labored breathing and focal pruritus were followed by death Macroscopic lesions were severe focal facial trauma, petechiae in cervicothoracic ganglia and dilated esophaguses. The medulla oblongata and the trigeminal, cranial cervical, cervicothoracic and parabronchial ganglia contained pseudorabies virus and pronounced nonsuppurative inflammatory changes. The neural distribution of lesions and virus suggests that the virus travelled from the respiratory mucosa to the central and sympathetic nervous system by two routes: 1) in the vagus and glossopharyngeal nerves to the medulla oblongata and 2) in the postganglionic fibers to the sympathetic ganglia. The presence of virus in the nasal mucus indicated that horizontal transmission of pseudorabies virus may occur among sheep.

Animals↗
PubMed1988

MK-801, a proposed noncompetitive antagonist of excitatory amino acid neurotransmission, produces phencyclidine-like behavioral effects in pigeons, rats and rhesus monkeys.

The behavioral effects of MK-801 [(+)-5-methyl-10,11-dihydroxy-5H-dibenzo(a,d)cyclohepten-5,10-imin e], a proposed noncompetitive N-methyl-D-aspartate (NMDA) antagonist, were compared to those of phencyclidine (PCP). In pigeons, MK-801 produced PCP-like catalepsy (i.e., loss of righting without eye closure and without muscle relaxation) and PCP-like discriminative stimulus effects. In rats, MK-801 produced PCP-like behavior (i.e., locomotion, sniffing, swaying and falling). In rhesus monkeys, like PCP, MK-801 produced 1) ketamine-like discriminative stimulus effects, 2) positive reinforcing effects and 3) ketamine-like anesthetic effects (i.e., anesthesia without eye closure and without respiratory depression, but with profuse salivation and with some muscle relaxation). Thus, MK-801 produced PCP-like behavioral effects in each species and with each procedure. MK-801 was 2 to 10 times more potent than PCP, depending on the effect measured and the species tested. Because MK-801 has been shown to have NMDA-antagonist properties, the findings of this study offer further support for the hypothesis that certain behavioral effects of PCP-like drugs may result from a reduction of neurotransmission at excitatory synapses utilizing NMDA-preferring receptors. The behavioral similarities between MK-801 and PCP make it relevant to evaluate PCP-like activity in clinical trials of MK-801.

Anesthesia↗