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Biomedical subjects

D E Hernandez

Publications and source records attributed to D E Hernandez.

At least 37 records · Page 2Linked to original sources
PubMed1987

Effect of hypophysectomy, adrenalectomy, pituitary hormone secretion and gastric acid secretion on neurotensin induced gastric protection against stress gastric lesions.

In previous studies we have established that intracisternal (i.c.) but not peripheral (intravenous) administration of neurotensin (NT), a brain and gastrointestinal tridecapeptide, totally prevents the development of gastric lesions produced by cold-restraint stress (CRS) with food-deprived rats. In this investigation, removal of the pituitary and adrenal gland, anterior pituitary hormone secretion and gastric acid secretion were evaluated independently as potential intermediates for NT's protective effect. NT (30 micrograms) produced a significant reduction of gastric lesions incidence and severity in intact and sham-operated controls. Adrenalectomy, but not hypophysectomy totally blocked the protective effect of i.c. NT. In addition, replacement therapy with s.c. prednisone (1 mg/kg) for 5 days following adrenalectomy did not restore the protective activity of central (i.c.) NT in adrenalectomized rats. A significant reduction of serum levels of TSH, PRL and GH following i.c. NT (30 micrograms) was observed after 2h of CRS. The gastrosecretory studies revealed that i.c. NT (30 micrograms) did not affect gastric acid secretion in pylorus ligated rats. However, blockade of peripheral (gut) cholinergic (muscarinic) receptors with i.p. atropine methylbromide (1 mg/kg) significantly raised gastric pH and reduced gastric acid concentration and output. In conclusion, the results of this study indicate that the acute protective effect of brain NT appears to be mediated, at least in part, by the sympathoadrenomedullary axis, and not by the pituitary gland or substances derived from the pituitary or by inhibition of gastric acid secretion.

Adrenalectomy↗
PubMed1987

Inhibition of gastric acid secretion by immunoneutralization of endogenous brain thyrotropin-releasing hormone.

Previous studies have shown that intracisternal (i.c.), but not intravenous administration of thyrotropin-releasing hormone (TRH), an endogenous tripeptide (pGlu-His-Pro-NH2), produces a time-, dose-dependent and vagus-mediated stimulation of acid secretion in rats. This study was designed to test the hypothesis that endogenous brain TRH plays a role in regulation of acid secretion in the pylorus-ligation model. In confirmation of previous reports, i.c. TRH (1 microgram) significantly (P less than 0.01) stimulated gastric acid output, gastric secretory volume and decreased gastric intraluminal pH. Intracerebroventricular (i.c.v.) infusion of TRH antiserum (anti-TRH) 30 min prior to pyloric occlusion significantly reduced acid output, secretory volume and raised gastric pH. This inhibitory gastric acid secretory response to i.c.v. anti-TRH appears to be specific since i.c.v. infusion of normal rabbit serum or antisera raised against neurotensin (NT), Leu-enkephalin (L-enk), gonadotropin-releasing hormone (GnRH), somatostatin (SRIF) and alpha-melanocyte stimulating hormone (alpha-MSH) were without measurable effect. The findings of this study indicate that endogenous brain TRH, but not NT, L-enk, GnRH, SRIF or alpha-MSH plays a physiological role in regulation of acid secretion.

Animals↗
PubMed1987

Reversal of pentobarbital-induced narcosis by thyrotropin-releasing hormone (TRH) in dogs.

A growing body of evidence suggests that thyrotropin-releasing hormone (TRH), and endogenous brain tripeptide, produces behavioral excitation in a variety of mammalian species. This study evaluated the cardiopulmonary and antidepressant response to a single intravenous (i.v.) bolus of TRH in sodium pentobarbital (33 mg.kg-1) anesthetized dogs. TRH (0.5 and 1 mg) produced a significant dose-dependent decrease in sleeping time (33% and 51%, respectively) when compared to i.v. vehicle (1 ml of 0.9% NaCl)-treated animals. Of interest was the finding that the high (1 mg), but not the low (0.5 mg) dose of TRH significantly (P less than 0.01) increased mean arterial pressure and heat rate. In addition, i.v. TRH (1 mg) significantly (P less than 0.01) decreased tidal volume. A trend toward increased respiratory frequency in TRH-treated dogs was noted, this difference, however, did not reach statistical significance. In conclusion, the results of this study support the view that TRH, and endogenous brain hormone, may have an important clinical application in cases where stimulation of the central nervous system is required.

Animals↗
PubMed1987

Involvement of dopamine receptors in experimental ulceration.

The purpose of this study was to characterize dopamine binding sites in gastric (mucosa and muscle) tissue and to examine changes of gastric dopamine receptors in response to variable periods of cold-restraint stress (CRS). Scatchard analysis of binding data in tissues of non-stressed animals revealed a single, homogeneous class of saturable high-affinity dopamine binding sites in gastric mucosa (Bmax = 21.3 pmol/mg protein; KD = 4 X 10(-7) M) and in gastric muscle (Bmax = 34 pmol/mg protein; KD = 0.6 X 10(-7) M). After 1 h of CRS, a time at which a low (30%) incidence of gastric ulcers was observed, the binding in mucosa had increased by 53%. Scatchard analysis revealed a significant increase in dopamine receptor number (Bmax = 37.6 +/- 7.0 versus 21.3 +/- 2.0 pmol/mg protein) and no significant change in affinity (KD = 6.8 +/- 1.6 versus 4 +/- 0.7 X 10(-7) M). No change in 3H-dopamine binding to muscle tissue was observed. These results indicate that up-regulation of mucosal dopamine receptors may precede the development of gastric ulcers.

Animals↗
PubMed1986

Involvement of brain dopamine systems on neurotensin-induced protection against stress gastric lesions.

We have previously demonstrated that intracisternal (i.c.) administration of neurotensin (NT), a brain and gastrointestinal tridecapeptide, potently inhibits gastric ulcer formation induced by cold-restraint stress (CRS) in rats. This study evaluated the effect of i.c. NT (17.9 nmol) or vehicle (10 microliter of 0.9% NaCl) on the development of CRS-induced gastric ulcers and on dopamine (DA) concentrations and DA turnover (DOPAC/DA) in selected brain regions after 0, 1, 2 and 3 h of CRS. As anticipated, and in confirmation of previous findings, NT significantly reduced the incidence and severity of CRS gastric ulcers in a time-dependent manner. Neurotensin significantly decreased DA concentration and DA turnover in the striatum. In the nucleus accumbens, however, NT produced a decrease in DA concentration and a concomitant increase in DA turnover after 2 and 3 h of CRS. No significant effects of brain NT on DA concentration and DA turnover were observed in the hypothalamus or olfactory tubercles. These findings suggest that the anti-ulcer effect of brain NT may be mediated, at least in part, by a differential activation of the mesolimbic and nigrostriatal DA systems.

Animals↗
PubMed1986

Neuroendocrine mechanisms of stress ulceration: focus on thyrotropin-releasing hormone (TRH).

It is generally accepted that stress ulceration, a multifactorial or pluricausal gastrointestinal disorder, may be the result of mechanistic interrelationships between mucosal, vascular, hormonal and neurogenic factors. The relative importance of each of these independent mechanisms remains unclear. This minireview represents an attempt to interpret many recent studies on certain neurogenic mechanisms and to integrate these observations into the existing body of knowledge. A variety of in vitro techniques and animal models to manipulate actual structures, organ systems, and certain well-defined hormonal influences have been utilized. The peripheral studies have followed, for the most part, the established observation that the stomach is under reciprocal control by sympathetic inhibitory and parasympathetic excitatory autonomic fibers. As a result, several autonomic adrenergic neurotransmitter substances have been found to promote mucosal resistance. Some of these include dopamine, epinephrine, and norepinephrine. Others in contrast, appear to promote vulnerability of the mucosa, and of these, the most well-studied include acetylcholine and histamine.

Animals↗
PubMed1986

Differential effects of intracisternal neurotensin and bombesin on stress- and ethanol-induced gastric ulcers.

This study evaluated the effect of intracisternal (I.C.) administration of the brain and gastrointestinal peptides neurotensin (NT) and bombesin (BOM) on the acute development of gastric ulcers induced by cold-restraint stress (CRS) and ethanol in rats. The results of this study can be summarized as follows: In confirmation of previous observations I.C. NT (30 micrograms) and BOM (1 microgram) significantly reduced gastric ulcer incidence and severity induced by 3h of CRS. The results of the ethanol preparation indicate that although I.C. BOM (1 microgram) significantly (P less than 0.05) increased intraluminal gastric pH and mucus, it did not prevent gastric ulcer formation. NT (30 micrograms), by contrast, was totally inactive in this ethanol model. These findings support a role for brain NT and BOM in protection against psycho-behavioral, but not chemical forms of ulcer-producing stress.

Animals↗
PubMed1986

Effect of dopamine agonists and antagonists on neurotensin-induced antinociception.

In previous reports, we have demonstrated that intracisternal (IC) administration of neurotensin (NT), an endogenous tridecapeptide, produces significant antinociception in a variety of analgesic tests, including the hot-plate test. In addition, many of the central nervous system effects of NT (i.e., hypothermia, gastric cytoprotection) appear to be mediated by brain dopamine (DA) systems. In this study, we evaluated the effect of selected DA agonists and antagonists on NT-induced antinociception in the hot-plate test with mice. Doses, route of administration, and pretreatment interval were determined from the available literature to significantly affect the incidence of DA-dependent behaviors. Pretreatment with chlorpromazine but not haloperidol significantly potentiated NT-induced antinociception. This potentiating effect of chlorpromazine appears not to be due to any intrinsic antinociceptive activity of this agent, chlorpromazine had no significant effect on hot-plate latencies when administered alone. The involvement of DA on NT-induced antinociception was further substantiated by the findings that pretreatment with several DA receptor agonists, including methylphenidate, apomorphine, and d-amphetamine, significantly antagonized the antinociceptive response to IC NT. None of these agents significantly altered the animal's response to the hot-plate when administered alone. The data furnished in the present report suggest that central DA circuits may be involved in the expression of NT-induced antinociception.

Analgesics↗
PubMed1985

Phospholipid liposomes potentiate the inhibitory effect of antidepressant drugs on immobility of rats in a despair test (constrained swim).

Male rats forced to swim in a cylinder assumed an immobile posture. Immobility was reduced by antidepressant drugs, such as imipramine, desimipramine, iproniazid and mianserin injected 24, 5 and again 1 h prior to behavioral testing. Subchronic (4, 7 and 10 days) treatment with sonicated preparations of bovine hypothalamic phospholipid liposomes potentiated the inhibitory effect of all antidepressant drugs in the despair test. Acute administration of phospholipid liposomes failed to influence the drug effect. Furthermore, neither subchronic nor acute administration of phospholipid liposomes per se modified the immobility in the despair test. It is possible that the action of phospholipid liposomes on the inhibitory effect of antidepressant drugs on immobility of rats in the despair test may depend on potentiation of antidepressant-induced change in the sensitivity of monoamine receptors in the brain.

Animals↗
PubMed1985

Role of brain neurotransmitters on neurotensin-induced gastric cytoprotection.

We have reported previously that intracisternal (IC) administration of neurotensin (NT) prevents stress-induced gastric ulcers in rats. This effect of NT appears to be mediated by the central nervous system because peripheral (IV) NT is totally ineffective. The present study sought to clarify the central mechanism of the cytoprotective effect of NT by utilizing pharmacological treatments which alter the function of brain neurotransmitter systems. Pretreatment with intracerebroventricular (ICV) administration of agonists and antagonists of acetylcholine (ACh), gamma-aminobutyric acid (GABA), and serotonin (5-HT) receptors or with an anti-opiate (naloxone) agent did not significantly alter NT-induced cytoprotection. However, pretreatment with ICV haloperidol, a dopamine (DA) receptor antagonist, totally blocked NT's cytoprotective effect. In addition, pretreatment with methylphenidate, a DA receptor agonist, produced cytoprotection similar to IC NT. These data indicate that NT-induced cytoprotection is not mediated by 5-HT, GABA, ACh (muscarinic) receptors, or endogenous opiate systems, but suggest interactions between brain DA systems and NT.

Animals↗
PubMed1985

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.

Animals↗
PubMed1985

Pupillary effects of neurotensin: structure-activity relationships.

We have previously reported that intracameral (I.C.) administration of neurotensin (NT) potently induces a time- and dose-dependent miosis in rabbits. This study was designed to determine structure-function relationships for NT-induced miosis. NT and twelve different fragments and analogs of NT, and the structurally-unrelated peptides beta-endorphin (beta-end), somatostatin (SRIF) and thyrotropin-releasing hormone (TRH) were tested in a dose equimolar to 30 micrograms of NT for their effects on pupillary diameter (PD) in rabbits. In confirmation of previous findings, NT produced significant miosis. Followed in order of duration of effect were D-Trp11-NT, D-Tyr11-NT, the N-terminal fragment NT1-12, [Gln4] - NT and NMe-NT. The N-terminal fragment NT1-8, D-Arg8-NT, and D-Phe11-NT were weakly active. In addition, the initial N-terminal fragment NT1-6 and the C-terminal fragments NT8-13 and NT9-13 did not affect PD. D-Pro10-NT, beta-end, SRIF, and TRH were totally ineffective. The results of this investigation contribute to support a role for NT on regulation of pupillary function, and suggest that the midportion of NT appears to be critical for the expression of NT-induced miosis.

Animals↗
PubMed1985

Role of the autonomic nervous system in the cytoprotective effect of neurotensin against gastric stress ulcers in rats.

Pharmacologic agents were used to study the role of the autonomic nervous system in the cytoprotection produced by intracisternal neurotensin against cold plus restraint stress-induced gastric ulcers in rats. Drugs which stimulated alpha- or beta-adrenergic receptors or blocked muscarinic cholinergic receptors reduced the incidence of ulcers to a similar degree as intracisternal neurotensin; alpha-adrenergic or beta-adrenergic blockade as well as cholinergic stimulation prevented neurotensin's beneficial effect. However, pretreatment with indomethacin blocked only the cytoprotective effect of neurotensin or beta-adrenergic stimulation, but not that of muscarinic cholinergic blockade. In addition, pretreatment with reserpine or guanethidine also was effective in preventing cytoprotection by intracisternal neurotensin. These data indicate that the mechanism for cytoprotection by centrally administered neurotensin is mediated at least in part through activation of the sympathetic nervous system. This activation by neurotensin appears to produce cytoprotection by stimulation of gastric mucosal prostaglandin synthesis.

Animals↗
PubMed1984

Prevention of stress-induced gastric ulcers by dopamine agonists in the rat.

Dopamine (DA) and DA agonists have been shown to exert a protective role against the formation of duodenal ulcers. The effect of stimulation of DA receptors on the development of stress-induced gastric ulcers is currently unknown. Accordingly, we evaluated the effect of several DA agonists on the development of gastric ulcers induced by 3 h of cold + restraint stress (CRS) in rats. Apomorphine, d-amphetamine, methylphenidate, and threo-dl-p-hydroxymethylphenidate (an hydroxylated analog of methylphenidate), significantly reduced both the incidence and severity of CRS-induced gastric ulcers. The gastric cytoprotection afforded by these agents was dose-related, and completely antagonized by pretreatment with the peripherally acting DA antagonist domperidone. Because domperidone blocks peripheral, but not central, DA receptors, and since the entry of threo-dl-p-hydroxymethylphenidate across the blood-brain barrier into the brain is restricted to a great extent, we conclude that stimulation of peripheral DA receptors is primarily involved in the gastric cytoprotection induced by dopamimetics.

Animals↗
PubMed1984

Evidence for biological activity of two N-terminal fragments of neurotensin, neurotensin1-8 and neurotensin1-10.

Intracisternal (i.c.) administration of the endogenous tridecapeptide neurotensin (NT) has been previously shown to significantly reduce the incidence of cold-restraint stress (CRS)-induced gastric ulcers in rats. In this study we confirm the cytoprotective activity of central NT, and document structure-activity relationships for this effect of NT. When tested in a dose equimolar to 17.9 nmol of NT the NT analogs [Gln4]NT, D-Trp11-NT, and D-Arg8-NT were cytoprotective, whereas D-Arg9-NT was not. Gonadotropin-releasing hormone (Gn-RH) and melanocyte-stimulating hormone-release inhibiting factor (MIF-1), two oligopeptides structurally unrelated to NT exhibited no cytoprotective efficacy in this paradigm. The C-terminal fragments of NT, xenopsin and NT8-13, and the N-terminal fragment NT1-6 were completely ineffective. Finally, NT1-8 and NT1-10, two N-terminal fragments of NT produced significant cytoprotective activity at this dose level. The cytoprotection afforded by NT1-8 and NT1-10, like that of NT, was dose-dependent with ED50's similar to that of NT (NT = 16.2 nmol, NT1-8 = 17.8 nmol and NT1-10 = 19.9 nmol). In conclusion, we demonstrate that smaller molecular weight forms of NT thought to be degradation products of NT can effectively exert biological effects.

Animals↗
PubMed1984

The role of the adrenal gland in cytoprotection against stress-induced gastric ulcers in rats.

Subcutaneous treatment with either prednisone or isoproterenol significantly prevented the development of cold plus restraint stress (CRS)-induced gastric ulcers in rats. The effect of each agent was dose-dependent. Bilateral adrenalectomy prevented isoproterenol, but not prednisone-induced gastric cytoprotection. However, prednisone (1 mg/kg X 5 days) restored the ability of isoproterenol to afford cytoprotection in adrenalectomized rats. Finally, inhibition of prostaglandin synthesis with indomethacin (5 mg/kg) totally abolished the cytoprotective response to both prednisone and isoproterenol in this CRS model. These results indicate that glucocorticoids modulate the cytoprotective effect of adrenal catecholamines, and that both adrenal glucocorticoids and catecholamines require an intact prostaglandin synthetic pathway for expression of their cytoprotective properties.

Adrenal Glands↗
PubMed1984

Mitogenic and mitogenically defective phytohemagglutinin isolectins stimulate T-cell growth factor (interleukin 2) production and response in fresh and cultured human T lymphocytes.

L4-PHA (L4) and E4-PHA (E4) lectins isolated from Phaseolus vulgaris have different mitogenic properties. The mechanisms of the differences in mitogenic behavior were sought in the interaction of lectin, lymphocyte subsets, and T-cell growt factor (TCGF) also known as interleukin 2 (IL-2). TCGF activity in culture supernatants ( L4S ; E4S ) from L4- and E4-stimulated, freshly isolated lymphocytes was assayed as stimulation of DNA synthesis in TCGF-dependent continuous T-cell cultures (CTC). E4S contained less TCGF than did L4S . Addition of partially purified TCGF does not increase the stimulation of fresh lymphocytes by L4 or E4. L4 and E4 equally stimulate both helper (OKT4+) and suppressor (OKT8+) cells. The ability of L4 to further stimulate CTC is slowly lost (15 greater than 30 greater than 45 days). It is concluded that production of TCGF is not rate limiting in E4 and L4 stimulation of lymphocytes. The growth of CTC, which requires the presence of TCGF, remains sensitive to, but not dependent on, L4 for at least 30 days.

Antibodies, Monoclonal↗