Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01185 (vasopressin)
 23,126 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The cardiovascular effects of opioid peptides have been studied. Leucine-enkephalin (Leu-ENK) produced blood pressure (BP) increases following administration into the lateral brain ventricles (i.v.t.), into the cisterna magna (i.c.i.), and following intravenous (i.v.) administration. Heart rate (HR) increases were observed following all routes of administration (threshold for BP and HR effects at 0.3 nmole, maximum at 360 nmoles). The cardiovascular effects were independent of generalized seizures, which may occur at higher doses of enkephalins (ENK). D-alanine-enkephalin (D-Ala-ENK) attenuated the vagal component of the baroreceptor reflex in cats. This was indicated by the findings that HR did not decrease following D-Ala-ENK-induced BP increases and that the compensatory decreases in HR following i.v. pressor doses of angiotensin II (ANG II) were markedly attenuated in cats treated with i.v.t. D-Ala-ENK. Naloxone inhibited the BP and HR effects following i.c.i. and i.v., but not following i.v.t., administration of Leu-ENK. The i.v.t. Leu-ENK effect were inhibited by beta-adrenergic receptor blockade. Bratteboro rats homozygous for hereditary diabetes insipidus with total absence of antidiuretic hormone (ADH) synthesis responded with BP decreases following i.v.t. Leu-ENK, while BP increases were observed in control Long-Evans rats. Blood pressure increases to i.v.t. Leu-ENK were markedly greater in spontaneously hypertensive rats of the stroke-prone strain (SHR-sp) than in normotensive control rats; SHR-sp exhibit a humoral pattern of increased ADH, ACTH, and catecholamines, presumably due to central peptidergic stimulation. The known effects of opioid peptides on these hormones and the observed cardiovascular responses suggest a possible participation of this peptide system in the maintenance of high BP in the SHR-sp.
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PMID:Enkephalin effects on blood pressure, heart rate, and baroreceptor reflex. 739 23

1. The cardiovascular effects of an enkephalin analogue were examined in spontaneously hypertensive and normotensive Wistar-Kyoto rats. (D-Ala2)-methionine enkephalin caused a biphasic increase in blood pressure and an increase in heart rate after intracerebroventricular injection. 2. The initial pressor response to (D-Ala2)-methionine enkephalin was greater in hypertensive than in normotensive rats. No difference was noted between groups during the secondary pressor response. Heart rate increases paralleled the secondary increase in blood pressure. 3. Naloxone pretreatment abolished the secondary increase in blood pressure and the tachycardia, but did not blunt the initial pressor response in female Wistar-Kyoto rats. 4. Plasma levels of arginine vasopressin were depressed during the plateau phase of the pressor response in hypertensive rats given intracerebroventricular (D-Ala2)-methionine enkephalin. 5. The results suggest that the cardiovascular effects of central enkephalin are not due to vasopressin, but may involve activation of the sympathetic nervous system.
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PMID:Increased pressor responsiveness to enkephalin in spontaneously hypertensive rats: the role of vasopressin. 744 62

Normonatremic and chronically hyponatremic rats were pretreated with naloxone (5 mg/kg) or isotonic (150 mM) NaCl, then were given i.v. injections of 2 M NaCl (2 ml) or were hemorrhaged (20 ml/kg). Baseline and post-stimulus blood samples were withdrawn through indwelling jugular venous catheters. Baseline levels of plasma vasopressin (AVP) and oxytocin (OT) were similar in both normonatremic and hyponatremic rats and did not change after naloxone pretreatment. Increases in plasma AVP and OT levels in response to both hypertonic saline and hemorrhage were markedly blunted in the hyponatremic rats compared to the normonatremic rats. Naloxone pretreatment caused augmented AVP and OT secretion in response to hypertonic saline stimulation and hemorrhage in both the normonatremic and hyponatremic rats; the magnitude of the naloxone augmentations in the hyponatremic rats were sufficient to normalize the OT response to hypertonic saline and both the OT and AVP responses to hemorrhage. Our results therefore suggest that endogenous opioids are likely involved in the inhibition of stimulus-induced AVP and OT release that accompanies chronic hypoosmolality.
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PMID:Naloxone disinhibits magnocellular responses to osmotic and volemic stimuli in chronically hypoosmolar rats. 773 98

We examined the role of endogenous opioids in cardiovascular and neurohormonal responses to intracerebroventricular (icv) endothelin-1 (ET-1) in conscious rabbits. With or without pretreatment with intravenous naloxone (1 mg/kg), the effects of icv ET-1 (25 pmol/kg) on cardiovascular and neurohormonal responses were examined. ET-1 (icv) caused significant increases in mean arterial pressure (MAP), renal sympathetic nerve activity (RSNA), plasma catecholamines, and vasopressin levels. Naloxone pretreatment significantly augmented the increases in MAP and RSNA induced by icv ET-1. To clarify the mechanism of these effects, we also examined the effects of naloxone and naloxone methobromide, which does not cross the blood-brain barrier, on baroreceptor reflex. Intravenous naloxone (1 mg/kg) attenuated the baroreflex sensitivity assessed by RSNA (Smax: -9.9 +/- 1.7 vs. -6.9 +/- 1.2, P < 0.01); however, intravenous naloxone methobromide failed to alter the baroreflex sensitivity. Furthermore, in sinoaortic-denervated rabbits, naloxone pretreatment did not affect the increase in MAP induced by (icv) ET-1. These results suggest that intravenous naloxone acts in the central nervous system to attenuate the baroreflex sensitivity, which might augment the increases in MAP and RSNA induced by icv ET-1 in conscious rabbits.
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PMID:Naloxone augments sympathetic outflow induced by centrally administered endothelin in conscious rabbits. 818 85

1. We set out to investigate whether the administration of naloxone alone, naloxone plus vasopressin (AVP) or naloxone plus alprazolam to patients with Cushing's syndrome would result in a blunted dynamic response of the pituitary-adrenal axis compared with normal volunteers. Cushing's syndrome is often difficult to diagnose. It would be helpful if new tests were available to help in the biochemical distinction between Cushing's syndrome and non-Cushing's syndrome patients. 2. Naloxone testing correctly distinguished all seven patients with Cushing's syndrome (four pituitary Cushing's, two adrenal adenomas, one ectopic ACTH) from normal. Six patients were distinguished by the per cent change of plasma ACTH from basal being less than the normal range of 10 volunteers. The seventh patient (a pituitary Cushing's) was distinguished by the per cent change from basal of plasma cortisol being less than the normal range. 3. Naloxone plus AVP testing of two of four patients with pituitary Cushing's showed a smaller per cent change for both ACTH and cortisol compared with five normal volunteers, correctly distinguishing Cushing's from the normals. 4. Naloxone plus alprazolam did not distinguish Cushing's from normal. 5. Naloxone testing and naloxone plus AVP testing appear to be promising methods of distinguishing Cushing's syndrome from normal. Further experience with these tests, especially with obese and pseudo-Cushing's individuals, will be necessary to determine their place in the diagnosis and differential diagnosis of the cause of Cushing's syndrome.
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PMID:New diagnostic tests for Cushing's syndrome: uses of naloxone, vasopressin and alprazolam. 880 May 90

Oxytocin (OXT), a neurohypophyseal hormone, has a wide range of behavioral effects outside its classic peripheral endocrine functions. OXT involvement in adaptive central nervous system processes has been demonstrated as an inhibitory, amnestic action on learning and memory in different paradigms. Because adaptation and learning are likely to be involved in the neural events leading to drug tolerance and dependence, the question logically arose whether OXT is able to influence the development of tolerance of and dependence on abused drugs. In this review, we summarize our results on the effects of OXT on opiate (including morphine, heroin, and the endogenous opiates beta-endorphin and enkephalin) tolerance and dependence, heroin self-administration, psychostimulant-induced behavioral changes, and behavioral tolerance and sensitization. The sites and mechanisms of action and the possible physiological role of OXT are also discussed. In the first part of this review the effects of exogenously administered OXT on both the acute and chronic behavioral effects of opiates and psychostimulants have been summarized. OXT inhibited the development of tolerance to morphine, heroin, beta-endorphin, and enkephalin, OXT also inhibited the development of cross-tolerance between the predominantly mu-agonist heroin and the predominantly delta-agonist enkephalin in mice. Naloxone-precipitated morphine withdrawal syndrome was also attenuated by OXT. Heroin self-administration was decreased by OXT administration in heroin-tolerant rats. OXT inhibited cocaine-induced exploratory activity, locomotor hyperactivity, and stereotyped behavior in rats and in mice. Behavioral tolerance to cocaine was also attenuated by OXT. On the contrary, OXT stimulated the development of behavioral sensitization to cocaine. OXT did not alter the stereotyped behavior induced by amphetamine. In the second series of experiments, the sites of action of OXT on drug-related behavior were investigated. Intracerebro-ventricular (ICV) and intracerebral (IC) administration of an OXT-receptor antagonist inhibited the effects of peripherally administered OXT on morphine tolerance, heroin self-administration, and cocaine-induced sniffing behavior. This suggests the central, intracerebral location of OXT target sites. Local IC microinjection of OXT in physiological doses into the posterior olfactory nucleus, tuberculum olfactorium, nucleus accumbens, central amygdaloid nucleus, and the hippocampus inhibited the development of tolerance to and dependence on morphine as well as cocaine-induced sniffing behavior and tolerance to cocaine. The physiological role of endogenous OXT in acute morphine tolerance has also been demonstrated, since OXT antiserum (ICV) and OXT-receptor antagonist (injected into the basal forebrain structures) potentiated the development of morphine tolerance. Finally, we investigated the possible mechanisms of action of OXT on drug related behavior. Both morphine tolerance and dependence, and cocaine administration, increased dopamine utilization in the mesencephalon and in the nucleus accumbens, respectively. OXT treatment decreased the alpha-methylparatyrosine-induced dopamine utilization in the mesencephalon and in the nucleus accumbens-septal complex. Chronic OXT treatment decreased the number of apparent binding sites of dopamine in the basal forebrain area. It also inhibited a cocaine-induced increase in dopamine utilization in the nucleus accumbens, but not in the striatum. In light of this information, it appears that OXT inhibits the development of opiate tolerance, dependence, and self-administration as well as the acute behavioral actions of and chronic tolerance to cocaine. This suggests the possible role of this neuropeptide in the regulation of drug abuse. Therefore, OXT may act as a neuromodulator on dopaminergic neurotransmission in limbic-basal forebrain structures to regulate adaptive CNS processes leading to drug addiction.
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PMID:Role of oxytocin in the neuroadaptation to drugs of abuse. 921 Feb 15

Stress or noxious stimuli of various kind may induce the fight-flight response. In this situation a number of physiological and behavioural adaptations leading to defense of the organism occur. At a central level increased activity in the noradrenergic locus coeruleus (LC) and an enhanced secretion of corticotrophin-releasing factor (CRF) and vasopressin produced in the paraventricular nucleus (PVN) integrate stress response. Here the existence of an opposite psycho-physiological pattern associated with relaxation and growth and which is activated by certain types of non-noxious stimuli and integrated by oxytocin is proposed. In support of this, administration of oxytocin to male and female rats gives rise to effects of antistress nature in particular after repeated administration. Thus a five day treatment period with oxytocin 1 mg/kg s.c. or 1 micro g/kg i.c.v gives rise to sedation, lowering of blood pressure, increased withdrawal latency in the tail flick test and also a decrease of corticosterone levels and a rise of certain vagally controlled hormones. Weight gain is also increased under certain conditions. These effects persist several weeks after administration of oxytocin and cannot be reversed by oxytocin antagonists when established, suggesting that secondary mechanisms have been activated. Naloxone temporarily reverses the increased withdrawal of the tail flick test suggesting that opioid mechanisms have been activated to cause this particular effect. In contrast the sedative and blood pressure lowering effect seems to be induced by an enhanced activity in central alpha 2 receptors. Oxytocin levels increase in blood and CSF after various kinds of non-noxious sensory stimulation such as touch, light pressure and warm temperature in both female and male rats. It is suggested that other types of non-noxious stimuli as well may increase oxytocin release. If so, a release of oxytocin could be responsible for not only the antistress effects occurring during lactation but also why relationships, social contact and networks may have health promoting effects in particular by preventing cardiovascular disease.
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PMID:Oxytocin linked antistress effects--the relaxation and growth response. 940 3

Myotonic dystrophy (DM) is an autosomal dominant disorder causing myotonia, progressive muscle weakness, and endocrine abnormalities including hypothalamic-pituitary-adrenal (HPA) axis hyperresponsiveness to CRH-mediated stimuli. This ACTH hyperresponsiveness appears directly related to the underlying genetic abnormality. Naloxone (Nal)-mediated CRH release causes ACTH release in normal humans and an ACTH hyperresponse in DM. Alprazolam (APZ) attenuates the ACTH release in response to Nal in normal individuals, probably by inhibiting CRH release. This study investigates the effects of APZ on Nal-induced HPA axis stimulation in DM. The ACTH response to Nal in DM subjects was significantly reduced by APZ. Despite this DM patients have a relative resistance to APZ inhibition of Nal-induced ACTH/cortisol release. APZ caused a smaller percentage reduction in AUC for ACTH in DM compared with controls. These findings provide further insight into the mechanism(s) of the HPA axis abnormalities in DM. In DM, there may be an increase in tonic opioid inhibition to CRH release with compensatory increases in stimulatory pathways. Alternatively, these patients may have a basal increase in pituitary vasopressin levels or an enhanced AVP/CRH synergistic mechanism at the level of the corticotroph.
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PMID:Inhibition of naloxone-stimulated adrenocorticotropin release by alprazolam in myotonic dystrophy patients. 966 54

The effects of opioid peptides on the osmotic release of neurohypophyseal hormones, arginine vasotocin (AVT) and mesotocin (MT), were determined in 2-day-old chicks. Experiment 1 examined the effect of a variety of doses of naloxone, an opioid antagonist, on chicks administered isotonic or hypertonic solution. Plasma osmolality in chicks administered hypertonic solution was significantly higher than that in groups administered isotonic solution. None of the doses of naloxone affected plasma osmolality in response to isotonic and hypertonic solution. Plasma levels of AVT increased in hypertonic solution and this response was further enhanced by naloxone injection as the doses increased. The hypertonic solution alone did not affect plasma levels of MT, but additional treatment with naloxone slightly increased plasma levels of MT. Experiment 2 examined the effect of DAMGO ([d-Ala(2), N-Me-Phe(4),Gly-ol]-enkepha lin), a specific mu receptor agonist. Relatively high plasma osmolality caused by hypertonic solution was not affected by additional treatment with DAMGO. Plasma levels of AVT in response to hypertonic solution and to additional treatment with naloxone were reduced by higher doses of DAMGO. Experiment 3 examined the effect of naloxone on chicks administered different concentrations of NaCl. Administration of hypertonic solution resulted in an increase in plasma osmolality and plasma levels of AVT. Naloxone administration enhanced the increase in plasma AVT levels in response to hypertonic solution. Experiment 4 examined the effect of naloxone on different kinds of hypertonic solution, 0.15 M NaCl, 1.5 M NaCl, 2.55 M urea, and 1.95 M sucrose. The increases in plasma osmolality resulting from the administration of the urea and sucrose solutions were the same as those in the chicks injected with 1.5 M NaCl. In sucrose-treated chicks, plasma levels of AVT increased in chicks administered naloxone but not in chicks injected with normal saline. In contrast, no significant changes in plasma levels of AVT were observed in urea treatment with or without naloxone. In Experiments 3 and 4, plasma levels of MT after administration of hypertonic solutions did not change. However, naloxone administration enhanced plasma levels of MT in osmotically stimulated chicks. The results of the present study suggest that opioid peptides attenuate the increase in plasma AVT and MT in hypertonic states.
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PMID:Effects of naloxone on neurohypophyseal peptide release by hypertonic stimulation in chicks. 1041 36

Endogenous opioids target noradrenergic locus ceruleus (LC) neurons and potently inhibit LC activity. Nonetheless, it has been difficult to demonstrate functional regulation of the LC-noradrenergic system by endogenous opioids because of the lack of effect of opiate antagonists. The present findings provide evidence that endogenous opioids regulate LC neuronal activity during the termination of a stressor. LC neuronal discharge was recorded from halothane-anesthetized rats before, during, and after hypotensive stress elicited by intravenous nitroprusside infusion. In naive rats, mean arterial blood pressure was temporally correlated with LC activity such that hypotension was associated with increased LC discharge and a return to the normotensive state was associated with a decrease in LC discharge below pre-stress values. After microinfusion of an antagonist of the stress neuropeptide corticotropin-releasing factor (CRF) into the LC, the increase in LC discharge associated with hypotension was prevented, whereas LC inhibition associated with termination of the challenge occurred at an earlier time and was of a greater magnitude. In contrast, microinfusion of naloxone into the LC completely abolished LC inhibition associated with termination of the stressor. Naloxone microinfusion did not prevent LC inhibition associated with hypertension produced by intravenous vasopressin administration, suggesting that endogenous opioids may be selectively engaged during the termination of hypotensive stress. These results provide evidence for a functional release of endogenous opioids within the LC. This action of endogenous opioids may serve to counterbalance excitatory effects of CRF on the LC-norepinephrine system, thereby limiting its activation by stress.
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PMID:Evidence for functional release of endogenous opioids in the locus ceruleus during stress termination. 1140 37


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