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Biomedical subjects

R Stancampiano

Publications and source records attributed to R Stancampiano.

At least 37 records · Page 2Linked to original sources

Penile erection and yawning induced by paraventricular NMDA injection in male rats are mediated by oxytocin.

The effect of N-methyl-D-aspartic acid (NMDA), (+-)-alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid (AMPA), or (+-)-trans-1-amino-1,3-cyclo-pentanedicarboxylic acid (ACPD) (5-60 ng in 0.3 microliter of saline) microinjected in the paraventricular nucleus of the hypothalamus on penile erection and yawning was studied in male rats. NMDA induced both penile erection and yawning in a dose-dependent manner. AMPA and ACPD also induced penile erection but less potently than NMDA, but were ineffective in causing yawning. NMDA effect on penile erection and yawning was prevented by (+)-MK-801 (0.05-0.1 mg/kg IP, 10 min before NMDA), by the oxytocin antagonist d(CH2)5Tyr(Me)-Orn8- vasotocin (50-100 ng ICV 10 min before NMDA), but not by haloperidol (0.1-0.5 mg/kg IP 10 min before NMDA). The results suggest that NMDA induces penile erection and yawning by increasing oxytocinergic transmission by acting in the paraventricular nucleus of the hypothalamus.

Animals↗

Effect of excitatory amino acid receptor antagonists on apomorphine-, oxytocin- and ACTH-induced penile erection and yawning in male rats.

The effect of excitatory amino acid receptor antagonists, (5R,10S)-(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclo-hepten-5, 10-imine hydrogen maleate ((+)-MK-801), (+/-)-3-(2-carboxy-piperazin-4-yl)-propyl-1-phosphonic acid (CPP), 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and (+/-)-2-amino-4-phosphonobutanoic acid (AP-4), on penile erection and yawning induced by subcutaneous apomorphine (80 micrograms/kg), intracerebroventricular (i.c.v.) oxytocin (30 ng) and adrenocorticotropin (ACTH)-(1-24) (10 micrograms) was studied in male rats. Intraperitoneal (0.1-0.4 mg/kg) and i.c.v. (10-50 micrograms) (+)-MK-801 prevented dose dependently the penile erection and yawning induced by the three drugs. The (+)-MK-801 effect coincided with the appearance of head weaving, body rolling, hyperlocomotion and ataxia. Haloperidol (0.5 mg/kg i.p.) antagonized the prevention by (+)-MK-801 of oxytocin responses. Penile erection but not yawning was also prevented by high, but not low doses of CPP and CNQX, which impaired motor performance, AP-4 was ineffective at all doses tested. The above compounds were ineffective when injected into the paraventricular nucleus of the hypothalamus, the brain area where apomorphine and oxytocin act to induce penile erection and yawning. The results suggest that excitatory amino acid transmission is not involved in the expression of penile erection and yawning induced by the above compounds.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

Hippocampal oxytocin mediates apomorphine-induced penile erection and yawning.

Repeated episodes of penile erection and yawning can be induced in male rats either by low doses of the dopaminergic agonist apomorphine or by oxytocin given systematically or into a lateral ventricle (ICV), respectively, or after microinjection of the two substances directly in the paraventricular nucleus (PVN) of the hypothalamus. These behavioral responses are prevented in a dose-dependent manner by the ICV administration of the potent oxytocin antagonist d(CH2)5Tyr(Me)-Orn8-vasotocin. In contrast, the PVN injection of d(CH2)5Tyr(Me)-Orn8-vasotocin (1-30 ng), while effective in preventing oxytocin effect, was unable to prevent apomorphine response. On the other hand, apomorphine-, but not oxytocin-induced penile erection and yawning was prevented by electrolytic lesion of the medial septum (MS). Such a lesion decreased oxytocin content by about 45% in the hippocampus. The above results suggest that the hypothalamic-hippocampal oxytocinergic pathway mediates apomorphine-induced penile erection and yawning and that oxytocin is involved at different levels in the CNS for the control of these behavioral responses.

Animals↗

Apomorphine- and oxytocin-induced penile erection and yawning in male rats: effect of pertussis toxin.

The effect of the intracerebroventricular (ICV) administration of pertussis toxin on penile erection and yawning induced by apomorphine and oxytocin was studied in male rats. Pertussis toxin (2 micrograms ICV) prevented the above behavioral responses to apomorphine (80 micrograms/kg SC) and oxytocin (30 ng ICV) on day 3 and 4, but not on day 0 and 1 after treatment. Oxytocin and apomorphine responses were restored on day 6. Similar results were obtained by microinjecting pertussis toxin (0.5 microgram) in the paraventricular nucleus of the hypothalamus, the most sensitive brain area for the induction of penile erection and yawning by oxytocin and apomorphine. The results suggest that G proteins are involved in the expression of above responses to apomorphine and oxytocin.

Animals↗

Proteolytic conversion of neurohypophyseal peptides by rat thymocytes: involvement of endopeptidases.

The proteolytic conversion of oxytocin and Arg8-vasopressin by purified rat thymocytes was studied at 37 degrees C and physiological pH 7.4. The formed peptide fragments were isolated by high performance liquid chromatography and characterized by amino acid analysis. When oxytocin was incubated with rat thymocytes, oxytocin 1-8 and oxytocin 1-7 were isolated. In contrast, only Arg8-vasopressin 1-8 was found when Arg8-vasopressin was incubated with thymocytes. The formation of oxytocin 1-8, oxytocin 1-7 and Arg8-vasopressin 1-8 was prevented partially by 10(-3) M phenylmethylsulfonyl fluoride and iodoacetamide, and abolished by 0.5 x 10(-3) M Zn2+ and Hg2+ ions and 10(-3) M o-phenanthroline, but not by 10(-5) M leupeptin, lima bean trypsin inhibitor, trasylol, captopril and phosphoramidon. 0.5 x 10(-3) M EDTA was without effect on the formation of oxytocin 1-8 and Arg8-vasopressin 1-8 but increased by about 30% the formation of oxytocin 1-7. The results suggest that proteases capable of metabolizing oxytocin and Arg8-vasopressin are localized in the thymocyte surface membrane. Since oxytocin and vasopressin are synthetized by thymic epithelial cells and exert several actions on thymocytes, these proteases may play a physiological role in the inactivation of neurohypophyseal peptides at the thymocyte level.

Amino Acids↗

Prevention by morphine of apomorphine- and oxytocin-induced penile erection and yawning: site of action in the brain.

The effect of morphine administered systemically or into the paraventricular nucleus of the hypothalamus (PVN) on penile erection and yawning induced either by oxytocin or by the dopaminergic agonist apomorphine was studied in male rats. Systemic morphine (0.5 to 5 mg/kg intraperitoneally [IP]) prevented in a dose-dependent manner penile erection and yawning induced by the intracerebroventricular injection (ICV) of oxytocin (30 ng) or by the subcutaneous (SC) administration of apomorphine (80 micrograms/kg). Morphine (0.1 to 5 micrograms), but not U-69,593 (5 micrograms), injected into the PVN 10 minutes before oxytocin or apomorphine, was found to be able to prevent penile erection and yawning induced by the unilateral PVN microinjection of oxytocin (10 ng) or apomorphine (50 ng). The morphine-induced prevention of these behavioral responses was abolished by pretreatment with naloxone (3 mg/kg IP) 15 minutes before morphine. The present results suggest that morphine prevents apomorphine- and oxytocin-induced penile erection and yawning by inhibiting the activity of oxytocinergic neurons through mu-type receptors in this hypothalamic nucleus.

Analgesics↗

Effect of apomorphine on oxytocin concentrations in different brain areas and plasma of male rats.

The effect of the dopamine (DA) agonist, apomorphine, on oxytocin concentrations in the hypothalamus, hippocampus, septum and plasma was studied in male rats. Apomorphine dose dependently increased the concentration of oxytocin in the plasma and hippocampus, the minimal effective dose being 80 micrograms/kg s.c., which induced a 65% increase in plasma and a 45% increase in the hippocampus. The maximal effect (210 and 125% above controls) was induced with 240 micrograms/kg s.c. In contrast, there was a significant decrease (32%) in the oxytocin concentration in the hypothalamus, but only after the highest doses of apomorphine, while no change was found in the septum. The apomorphine effect in the hippocampus and hypothalamus was prevented by the mixed DA D-1/D-2 receptor blocker, haloperidol (0.3 mg/kg i.p.), and by the DA D-2 receptor blocker, (-)-sulpiride (20 mg/kg i.p.), but not by the DA D-1 receptor blocker, SCH 23390 (0.2 mg/kg s.c.). Similar effects were found in plasma, although SCH 23390 inhibited the apomorphine effect by 45%. Our results suggest that apomorphine stimulates oxytocinergic transmission in male rats and provide biochemical support for the hypothesis that a DA-oxytocin link exists in the central nervous system.

Animals↗

Oxytocin-induced penile erection and yawning: role of calcium and prostaglandins.

The effect of verapamil, flunarizine, nimodipine, nicardipine, and nifedipine, calcium channel inhibitors, and of indomethacin and aspirin, inhibitors of prostaglandin synthesis, on penile erection and yawning induced by oxytocin was studied in male rats. All calcium channel inhibitors given intraperitoneally (IP) 60 min before the intracerebroventricular (ICV) injection of oxytocin (30 ng) prevented in a dose-dependent manner oxytocin effect. Nimodipine and nicardipine were the most effective being active at doses between 5 and 20 mg/kg, while the others were active at doses higher than 15 mg/kg. Prevention of oxytocin effect was also seen after ICV injection of the above compounds. Unlike calcium channel inhibitors, indomethacin given either IP (10 and 50 mg/kg) or ICV (50 micrograms), or aspirin (100 mg/kg IP) were ineffective. Microinjection of calcium, but not of prostaglandin E2 and prostaglandin F2 alpha in the paraventricular nucleus of the hypothalamus, the brain area most sensitive for the induction of the above behavioral responses by oxytocin, induced a symptomatology similar to that induced by oxytocin. The present results suggest that calcium might be the second messenger which mediates the expression of penile erection and yawning induced by oxytocin.

Animals↗

Omega-conotoxin prevents apomorphine- and oxytocin-induced penile erection and yawning in male rats.

The effect of the intracerebroventricular (ICV) administration of omega-conotoxin GVIA on penile erection and yawning induced by oxytocin or by the dopaminergic agonist apomorphine was studied in male rats. The peptide toxin, 1-10 ng given ICV 5 min before oxytocin (30 ng ICV) or apomorphine (80 micrograms/kg SC), but not its carboxymethylated (CM) derivative, prevented the above behavioral responses in a dose-dependent manner. Similarly, omega-conotoxin (5 ng) unilaterally injected in the paraventricular nucleus of the hypothalamus (PVN) prevented penile erection and yawning induced by the microinjection of oxytocin (10 ng) or apomorphine (50 ng) in the PVN. omega-Conotoxin injected in the PVN, but not in the preoptic area, prevented also penile erection and yawning induced by systemic apomorphine (80 micrograms/kg SC). ICV omega-conotoxin was unable to prevent stereotypy induced by apomorphine (500 micrograms/kg SC). The present results provide further evidence that calcium plays a major role in the expression of penile erection and yawning and that apomorphine and oxytocin induce these behavioral responses by mobilizing calcium through omega-conotoxin-sensitive (N-type) calcium channels.

Animals↗

Role of calcium in the expression of ACTH-induced stretching, yawning and penile erection.

The effect of omega-conotoxin GVIA, a potent and selective inhibitor of N-type calcium channels and of the organic calcium channel inhibitors nimodipine, verapamil and flunarizine, on stretching, yawning and penile erection induced by ACTH 1-24 was studied in male rats. omega-Conotoxin (1-10 ng ICV 15 min before ACTH, 10 micrograms ICV), but not carboxymethylated omega-conotoxin, induced a dose-dependent prevention of all ACTH effects. In contrast, organic calcium channel inhibitors (20 mg/kg IP 30-60 min before ACTH) failed to modify ACTH-induced stretching and yawning but induced a 25% decrease in the number of penile erection episodes induced by the peptide, and prevented, like ICV omega-conotoxin, oxytocin- and apomorphine-induced yawning and penile erection. When injected in the paraventricular nucleus of the hypothalamus, omega-conotoxin prevented the above behavioral responses induced by apomorphine and oxytocin but not by ACTH 1-24. The present results suggest that ACTH induces stretching, yawning and penile erection by mobilizing calcium through central omega-conotoxin-sensitive calcium channels in brain sites different from those sensitive to oxytocin and apomorphine.

Animals↗

Effects of neonatal and adult thyroid dysfunction on thymic oxytocin.

Prenatal plus neonatal administration of methimazole (MMI), a procedure provoking marked hypothyroidism in rats, increased by about 100% the thymic content of oxytocin and severely (by approximately 80%) decreased the thymus weight, compared to euthyroid counterparts. Adult-onset, propylthiouracyl (PTU)-induced hypothyroidism, while provoking thymic involution, or thyroxine (T4) hyperthyroidism, did not affect oxytocin concentrations. Thymic involution and increases in thymus oxytoxin could also be obtained with repeated administration of the potent glucocorticoid dexamethasone. However, since corticosterone, unless subchronically injected at largely supraphysiological doses, was previously shown to have no influence on thymic parameters of young adult rats, a major involvement of the neonatal adrenal axis in oxytocin alterations could be excluded. It is suggested that the ontogenesis of thymic oxytocin production is under thyroid control.

Aging↗

Oxytocin-induced motor disturbances: relationship with penile erection and yawning.

The intracerebroventricular (ICV) injection of oxytocin at doses between 5 and 100 ng induced repeated episodes of penile erection and yawning, while at doses between 100 ng and 10 micrograms it induced motor disturbances often culminating in barrel rotation in rats. The intensity of motor disturbances was inversely correlated to the number of yawning and penile erection episodes. Pretreatment with the dopaminergic agonist apomorphine (80 and 240 micrograms/kg SC) failed to modify the incidence of motor disturbance induced by high doses of oxytocin, but markedly reduced the intensity of the symptomatology in a dose-dependent manner. The present results suggest that high doses of oxytocin induce motor disturbances which mask penile erection and yawning, and that brain dopaminergic systems have a protective role against this symptomatology.

Animals↗

Circulating immune complexes in patients with usual interstitial pulmonary fibrosis: partial characterization and relationship with Thermoactinomyces vulgaris.

Sixty-six sera were analysed by solid-phase conglutinin binding assay, to detect the levels of circulating immune complexes (CIC), and by enzyme-linked immunosorbent assay (ELISA) to show a correlation with antibodies to Thermoactinomyces vulgaris. Sixty per cent of patients with usual interstitial pulmonary fibrosis (UIP), were positive for CIC; and T. vulgaris antibodies were detected in 60% of the same patients. In comparison, there was a low frequency of positive results in bronchitis patients (5% for CIC and 35% for T. vulgaris), and in normal blood donors (0% for CIC and 30% for T. vulgaris). Furthermore 31% of patients with lung cancer were found positive for CIC, but not for T. vulgaris. Immune complexes purified on Protein A-Sepharose and by sucrose density gradient from patients with UIP, showed a sedimentation coefficient higher than 19 S. The purified material was found to contain IgG and IgM as antibodies. Binding of immune complexes, purified by sedimentation on sucrose gradient, to conglutinin was inhibited by the presence of T. vulgaris antigen; thus suggesting that this antigen might be present in the complexes.

Antibodies, Bacterial↗

Penile erection and yawning induced by oxytocin and related peptides: structure-activity relationship.

The potency of several oxytocin-related peptides in inducing penile erection and yawning after injection into a lateral ventricle of male rats was compared. Substitution of two amino acids in the oxytocin molecule or deletion of the C-terminal glycinamide as in des-GlyNH2-oxytocin [oxytocin(1-8)] reduced oxytocin potency in inducing both effects, the rank order being: oxytocin greater than [Thr4,Gly7]-oxytocin congruent to isotocin [( Ser4,Ile8]-oxytocin) greater than vasopressin [( Phe3,Arg8]-oxytocin) greater than des-GlyNH2-oxytocin. Oxytocin's ability to induce penile erection and yawning was abolished by permanent opening of the disulfide bridge by reduction and carboxymethylation. Oxytocin(1-6) and oxytocin(7-9) were also inactive. Penile erection and yawning induced by oxytocin-related peptides were antagonized in a dose-dependent manner by nonapeptide antagonists with a rank order of potency that follows their antioxytocic activity (d[(CH2)5Tyr(Me)Orn8]-vasotocin congruent to [Pen1,Phe(Me)2,Thr4,Orn8]-oxytocin greater than d[(CH2)5Tyr(Me)Arg8]-vasopression). Carboxymethylated oxytocin, oxytocin(1-6), and oxytocin(7-9) were devoid of antagonistic activity. The present results suggest that central oxytocin receptors mediating the expression of penile erection and yawning are structurally related to those present in the uterus and in the mammary gland.

Animals↗

Hypothalamic modulation of immunoreactive oxytocin in the rat thymus.

Immunoreactive oxytocin was determined in a peptidic extract of rat thymus by means of a highly specific radioimmunoassay combined with high pressure liquid chromatography fractionation. Rat thymus was found to contain 80 +/- 7.5 pg/g wet tissue (congruent to 0.56 pg/mg protein) of oxytocin-like immunoreactivity, which behaved like synthetic oxytocin in the radioimmunoassay and in two different high pressure liquid chromatography columns. Oxytocin concentration was increased by bilateral electrolytic lesion of the paraventricular nucleus of the hypothalamus (PVN), and by high doses of corticosterone (10 mg/kg IM for 7 days) but was not modified by low doses of corticosterone (1 mg/kg IM for 7 days) or by hypophysectomy. The results suggest that rat thymus synthesizes oxytocin and that thymic oxytocin concentration is modulated by the hypothalamus.

Animals↗