κ-Opioid modulation of vasopressin secretion in conscious rats

1991 ◽  
Vol 129 (3) ◽  
pp. 411-416 ◽  
Author(s):  
T. Wells ◽  
M. L. Forsling
Keyword(s):  
Plasma Concentration ◽  
Receptor Agonist ◽  
Plasma Concentrations ◽  
Endogenous Opioids ◽  
Inhibitory Influence ◽  
Conscious Rat ◽  
Opioid Receptor Agonist ◽  
Basal Plasma ◽  
Vasopressin Secretion ◽  
Prior Administration

ABSTRACT A series of studies has been performed in the conscious rat to investigate the effect of the intracerebroventricular (i.c.v.) administration of the selective κ-opioid receptor agonist, U50 488H, on arginine vasopressin (AVP) secretion stimulated by i.c.v. administration of hypertonic NaCl. Similarly, the effect of the i.c.v. administration of morphine and the i.v. administration of naloxone on AVP secretion was investigated. The response of AVP to an i.c.v. injection of hypertonic NaCl was potentiated by naloxone at a dose of 0·4 mg/kg, but a higher dose (1·2 mg/kg) was required to increase the basal plasma concentration of AVP. Prior treatment with U50 488H or morphine attenuated the increase in plasma concentrations of AVP stimulated by i.c.v. injection of hypertonic NaCl from 13·92±4·44 to 1·22±0·34 and 1·78±0·74 pmol/l respectively (n = 7; P<0·05). Prior administration of U50 488H also attenuated the potentiating effect of naloxone on AVP secretion stimulated by i.c.v. injection of hypertonic NaCl. These results indicate that basal AVP secretion is under tonic inhibitory control by dynorphin, and that μ-and κ-opioid receptors mediate an inhibitory influence of endogenous opioids on osmoreceptor-mediated AVP secretion. Journal of Endocrinology (1991) 129, 411–416

Comparative Analgesic and Mental Effects of Increasing Plasma Concentrations of Dexmedetomidine and Alfentanil in Humans

2004 ◽  
Vol 101 (3) ◽  
pp. 744-752 ◽  
Author(s):  
Martin S. Angst ◽  
Bhamini Ramaswamy ◽  
M Frances Davies ◽  
Mervyn Maze
Keyword(s):  
Plasma Concentration ◽  
Receptor Agonist ◽  
Plasma Concentrations ◽  
Analgesic Efficacy ◽  
Intrathecal Administration ◽  
Experimental Models ◽  
Sedation Score ◽  
Systemic Administration ◽  
Double Blind ◽  
Cognitive Speed

Background In animals, systemic and intrathecal administration of the alpha2 -adrenergic receptor agonist dexmedetomidine results in robust antinociceptive effects in models of heat pain. In humans, systemically administered dexmedetomidine is approved for sedating patients in the intensive care unit. However, whether systemic administration of dexmedetomidine in humans produces significant analgesia at doses causing sedation but not unconsciousness remains controversial. Methods This study in human volunteers used a placebo-controlled, double-blind, and randomized design to examine whether dexmedetomidine at doses causing mild to severe sedation produces analgesia in experimental models of heat and electrical pain. Results were compared to the effects of the mu-opioid receptor agonist alfentanil. A computer-controlled infusion provided four median step-up plasma concentrations of dexmedetomidine (0.09, 0.24, 0.54, and 1.23 ng/ml) and alfentanil (13.4, 33.8, 67.8, and 126.1 ng/ml). Results Sedative and cognitive effects of dexmedetomidine were dose-dependent, resulting in a median sedation score of 95 of 100 and slowing of cognitive speed (reaction time, trail-making test) by a factor of about two at the highest plasma concentration. Dexmedetomidine did not attenuate heat or electrical pain. Alfentanil caused severe sedation (median sedation score 88 of 100) and slowed cognitive speed by a factor of approximately 1.4 at the highest plasma concentration. Alfentanil attenuated heat and electrical pain dose dependently. Conclusion This study documents that systemic dexmedetomidine lacks analgesic efficacy for heat and electrical pain at doses causing mild to severe sedation. These results provide further evidence suggesting that systemic administration of dexmedetomidine lacks broad analgesic activity in models of acute pain at doses not rendering humans unconscious.

Changes in the hypothalamic contents of LHRH-I and -II and in pituitary responsiveness to synthetic chicken LHRH-I and -II during the progesterone-induced surge of LH in the laying hen

1990 ◽  
Vol 127 (3) ◽  
pp. 487-496 ◽  
Author(s):  
S. C. Wilson ◽  
R. A. Chairil ◽  
F. J. Cunningham ◽  
R. T. Gladwell
Keyword(s):  
Plasma Concentration ◽  
Pituitary Gland ◽  
Laying Hens ◽  
Plasma Concentrations ◽  
Posterior Hypothalamus ◽  
Anterior Hypothalamus ◽  
Significant Fall ◽  
Basal Plasma

ABSTRACT The contents of LHRH-I and -II in the anterior hypothalamus and posterior hypothalamus (including the mediobasal hypothalamus and median eminence) were measured at 90, 180 and 360 min after the i.m. injection of laying hens with progesterone. Whilst no changes were observed in the content of LHRH-I in the anterior hypothalamus, LHRH-I in the posterior hypothalamus tended to fall at 90 and 180 min after injection of progesterone in hens maintained on 16 h light:8 h darkness (16L:8D) and 8L:16D respectively. Pretreatment of laying hens with tamoxifen significantly increased the hypothalamic contents of LHRH-I and -II, raised the basal plasma concentration of LH and modified the LH response to progesterone injection. In hens in which tamoxifen prevented an increase in the plasma concentration of LH after progesterone injection, the content of LHRH-I in the posterior hypothalamus remained unchanged. In contrast, in hens in which progesterone stimulated a steep increase in LH within 90 min, there was a pronounced and significant fall in LHRH-I content of the posterior hypothalamus. No change in the hypothalamic content of LHRH-II was observed during the progesterone-induced surge of LH until plasma concentrations had attained maximal values or started to decline. Then, in hens maintained on 16L:8D, a significant fall in the content of LHRH-II in the anterior hypothalamus was found at both 180 and 360 min after injection with progesterone. Tests in vitro and in vivo of the responsiveness of the pituitary gland to synthetic LHRH-I and -II revealed no change at 90 min after injection of laying hens with progesterone, when plasma concentrations of LH were increasing, but a pronounced reduction when plasma LH concentrations were maximal or falling. These results suggest that LHRH-I mediates in the progesterone-induced increase in the plasma concentration of LH. Although the subsequent decline in plasma LH was associated with a reduced responsiveness of the pituitary gland to LHRH, a significant correlation between the contents of LHRH-I and -II in the anterior hypothalamus and a fall in the hypothalamic content of LHRH-II when plasma LH was maximal or declining allows the possibility of an involvement of this peptide in the neuroendocrine events preceding ovulation. Journal of Endocrinology (1990) 127, 487–496

Influence of opioid peptides on release from vasopressin and oxytocin neurones of the hypothalamoneurohypophyseal system: effects of naloxone in the conscious rat

1990 ◽  
Vol 68 (5) ◽  
pp. 568-574 ◽  
Author(s):  
Savio W. T. Cheng ◽  
Edward F. O'Connor ◽  
William G. North
Keyword(s):  
Plasma Concentration ◽  
Opioid Peptides ◽  
Plasma Concentrations ◽  
Plasma Osmolality ◽  
Plasma Sodium ◽  
Endogenous Opioid ◽  
Salt Loading ◽  
Conscious Rats ◽  
Basal Plasma ◽  
Acute And Chronic Treatments

We examined the effects of acute and chronic treatments with naloxone on release of vasopressin and oxytocin from the hypothalamoneurohypophyseal system (HNS) in conscious, chronically instrumented Long–Evans rats. Plasma concentrations of vasopressin-associated neurophysin and oxytocin-associated neurophysin were evaluated before and during an intravenous infusion of 18% saline at 100 μL∙kg−1 body weight∙min−1 for 60 min. Acute treatment with naloxone (2.75 μmol/kg, intravenous) did not measurably alter basal plasma osmolality or vasopressin-associated neurophysin concentration, but it caused a three-fold rise in basal plasma oxytocin-associated neurophysin concentration (16 ± 2 to 46 ± 3 fmol/mL, p < 0.005). Chronic treatment with naloxone (13.75 μmol/day, subcutaneous pellets) increased plasma osmolality (292 ± 1 to 300 ± 2 mosmol/kg H2O, p < 0.01) by day 5, but it had no measurable effects on basal vasopressin- or oxytocin-associated neurophysin concentration. There were also no significant differences in plasma sodium concentration (144.8 ± 1.1 vs. 142.2 ± 1.4 mequiv./L) under both conditions. Acute and chronic treatments with naloxone accompanied by salt loading produced a five- and four-fold decrease in the rates that plasma concentration of vasopressin-associated neurophysin changed with plasma osmolality, compared with untreated salt-loaded control rats. For oxytocin secretion from the HNS, both treatments accompanied by salt loading substantially decreased the threshold for changes in relation to plasma osmolality; the rise in plasma concentration of oxytocin-associated neurophysin was similar at all levels of hyperosmotic stimulation. A strongly correlated relationship between plasma oxytocin-associated neurophysin and plasma osmolality (r = 0.739) found for control animals became poorly correlated following treatments (acute, r = 0.173; chronic, r = −0.079). Our results suggest that in conscious rats, endogenous opioid peptides enhance the secretion of vasopressin from neurones of the HNS in response to hyperosmotic stimulation but inhibit both basal and stimulated release of oxytocin.Key words: naloxone, vasopressin, oxytocin, neurophysin, conscious rats.

Effect of naloxone on oxytocin and vasopressin release during vaginocervical stimulation in the goat

1987 ◽  
Vol 115 (2) ◽  
pp. 317-322 ◽  
Author(s):  
J. R. Seckl ◽  
S. L. Lightman
Keyword(s):  
Cerebrospinal Fluid ◽  
Plasma Concentrations ◽  
Random Order ◽  
Endogenous Opioids ◽  
Opioid Antagonist ◽  
Vasopressin Release ◽  
Peptide Release ◽  
Basal Plasma ◽  
Series Of Experiments

ABSTRACT We have investigated the secretion of oxytocin and arginine vasopressin (AVP) during vaginocervical stimulation in the conscious goat and examined the effect of the opioid antagonist naloxone on peptide release to this stimulus. Goats were implanted with guide tubes overlying the cisterna magna under anaesthesia and allowed to recover. Vaginocervical stimulation for 60 s resulted in a marked (P < 0·01) release of oxytocin into the plasma but neither plasma AVP nor cerebrospinal fluid (CSF) concentrations of oxytocin changed significantly. In a second series of experiments, unoperated goats were infused with saline or naloxone (4 mg bolus + 12 mg/h) in random order on two separate occasions. Infusion of naloxone had no effect on basal plasma concentrations of oxytocin or AVP. There was a marked and significant (P < 0·01) potentiation of oxytocin secretion following vaginocervical stimulation in animals infused with naloxone. Naloxone-infused animals showed a significant (P < 0·01) rise in plasma AVP after stimulation but plasma AVP did not change in the saline-infused controls. We conclude that vaginocervical stimulation leads to the selective release of oxytocin from the neurohypophysis without affecting concentrations of oxytocin in the CSF. Endogenous opioids inhibit the stimulated secretion of oxytocin and AVP in vivo in response to vaginocervical stimulation in the goat. J. Endocr. (1987) 115, 317–322

Relationship between oxytocin release and amplitude of oxytocin cell neurosecretory bursts during suckling in the rat

1987 ◽  
Vol 114 (2) ◽  
pp. 263-270 ◽  
Author(s):  
C. Meyer ◽  
M. J. Freund-Mercier ◽  
Y. Guerné ◽  
Ph. Richard
Keyword(s):  
Plasma Concentration ◽  
Direct Relationship ◽  
Plasma Concentrations ◽  
Pulsatile Release ◽  
Oxytocin Release ◽  
Anaesthetized Rats ◽  
Basal Plasma ◽  
Cell Firing ◽  
Basal Concentration

ABSTRACT Plasma concentrations of oxytocin and vasopressin were measured in relationship to oxytocin cell firing during suckling in urethane-anaesthetized rats. Preliminary experiments showed that plasma concentrations of oxytocin and vasopressin, which were increased immediately after anaesthesia, reverted to basal concentrations 3 h later. Moreover, it was found that exogenous oxytocin had entirely disappeared 5 min after i.v. bolus injections of known doses of oxytocin. Suckling did not modify the basal plasma concentration of oxytocin (14·6 ± 2·9 compared with 14·±61·5 pmol/l before suckling) except during a brief period immediately after neurosecretory bursts on oxytocin cells (37·8 ± 5·2 pmol/l; P < 0·001, n = 11). The plasma concentration of oxytocin did not differ significantly from the basal concentration 1·5 min later. The plasma concentration of vasopressin never varied. After two neurosecretory bursts of similar amplitude (total number of spikes during the burst) recorded on the same oxytocin cell, the variations in plasma concentration of oxytocin were also similar. When, for a given cell, the amplitude of neurosecretory bursts increased or decreased, the amount of oxytocin released changed in the same way. These data demonstrate (1) that suckling induces pulsatile release of oxytocin without vasopressin, and (2) a direct relationship between the amounts of oxytocin released and the amplitude of oxytocin cell neurosecretory bursts which argue in favour of simultaneous increases or decreases in the neurosecretory burst amplitudes on all oxytocin cells. J. Endocr. (1987) 114, 263–270

scholarly journals MAC-Sparing Effect of Transdermal Fentanyl in Sevoflurane-Anesthetized Sheep

2018 ◽  
Vol 68 (2) ◽  
pp. 211-216
Author(s):  
Duffee Lauren ◽  
Passino Sanna Eraldo ◽  
Scanu Antonio ◽  
Columbano Nicolò
Keyword(s):  
Receptor Agonist ◽  
Minimum Alveolar Concentration ◽  
Plasma Concentrations ◽  
Electrical Current ◽  
Minimal Effect ◽  
Fentanyl Patch ◽  
Transdermal Fentanyl ◽  
Opioid Receptor Agonist ◽  
Μ Opioid Receptor ◽  
Sparing Effect

Abstract Transdermal fentanyl allows for consistent plasma concentrations of a potent synthetic μ-opioid receptor agonist and can provide constant post-operative analgesia for up to 72 h. The aim of this study was to determine the reduction of the minimum alveolar concentration of sevoflurane (MACSEVO) by transdermal fentanyl in nonpregnant ewes. Nine sheep were mask induced with sevoflurane (SEVO in oxygen). MACSEVO determinations involved electrical current applied to the lateral metacarpus as a supramaximal stimulus and measurements in duplicate. Seven days later, a fentanyl patch (75 μg/h) was applied to each sheep and 15.1 ± 1.8 h later the MAC re-determined (MACSF). MACSF was 1.99 ± 0.32 %, corresponding to 25.6 ± 8.1 % reduction from MACSEVO (P < 0.001). Transdermal fentanyl produces a significant MACSEVO-sparing effect with minimal effect on cardiovascular parameters.

INFLUENCE OF METYRAPONE ON PLASMA CONCENTRATIONS OF TESTOSTERONE AND ANDROSTENEDIONE IN MAN

1971 ◽  
Vol 68 (3) ◽  
pp. 576-584 ◽  
Author(s):  
K. O. Nilsson ◽  
B. Hökfelt
Keyword(s):  
Body Weight ◽  
Male Patient ◽  
Gradual Increase ◽  
Plasma Concentrations ◽  
Plasma Testosterone ◽  
Testosterone Levels ◽  
Basal Plasma ◽  
Normal Males ◽  
A Minor ◽  
Secondary Hypogonadism

ABSTRACT Metyrapone was administered either orally, 750 mg every four h, in a total of six doses, or intravenously 30 mg per kg body weight as a four h infusion. In three males with normal endocrine functions, metyrapone given orally or intravenously induced a fall in plasma testosterone and an elevation of androstenedione within 2–8 h. When metyrapone was administered to a patient given dexamethasone to suppress endogenous ACTH production, the androstenedione levels did not alter whereas the testosterone levels showed a slight, transient decrease. In two normal females metyrapone administration was followed by a marked increase in plasma androstenedione whereas testosterone showed only a minor, gradual increase. In one male patient with Addison's disease the basal plasma testosterone was normal whereas the level of androstenedione was low. Following metyrapone intravenously, there was a slight suppression of plasma testosterone but no change in the androstenedione concentration. In one patient with primary hypogonadism, two with secondary hypogonadism and two with Klinefelter's syndrome the plasma testosterone was low under basal conditions and did not change following metyrapone. Basal plasma androstenedione was within the range for normal males and increased markedly following metyrapone in all the cases.

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