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Biomedical subjects

I Oye

Publications and source records attributed to I Oye.

At least 19 recordsLinked to original sources
PubMed1992

Naloxone counteracts the fast development of tolerance to morphine in guinea-pig ileum.

The ability of naloxone to inhibit the fast development of tolerance to morphine was examined in the guinea-pig ileum preparation. Dose-response curves were obtained either non-cumulatively with morphine alone or cumulatively with morphine alone and in combination with different concentrations of naloxone. We present some theoretical considerations concerning the competitive interaction between agonist and antagonist on a receptor. According to these theories, it is possible to perform dose-response experiments for an agonist in combination with different concentrations of antagonist and extrapolate to the dose-response curve for agonist alone and to the dissociation constant for the antagonist. EC50 values for morphine alone obtained either non-cumulatively or by extrapolation are almost identical and are significantly lower than those obtained cumulatively. The results indicate that tolerance develops very quickly when dose-response curves are obtained cumulatively with morphine alone and that low concentrations of naloxone counteract the development of tolerance.

Animals↗
PubMed1992

Effects of ketamine on sensory perception: evidence for a role of N-methyl-D-aspartate receptors.

The chiral forms of ketamine were applied as probes for N-methyl-D-aspartate receptor-mediated neurotransmission in humans. Both enantiomers, in clinically relevant concentrations, displaced [3H]dizocilpine (MK 801) from specific binding sites (phencyclidine sites) in membrane fractions of brain homogenates. (S)-Ketamine was at least 4 times as potent as (R)-ketamine in this respect. In healthy volunteers, the most obvious effect of subanesthetic doses of both enantiomers was altered sensory perception. (S)-Ketamine was 4 times as potent as (R)-ketamine in reducing pain perception and in causing auditory and visual disturbances. Both enantiomers caused proprioceptive disturbances (feelings of detachment from the body) and slightly reduced the ability to recall objects seen after administration of the drugs. The ability to recall objects seen immediately before drug exposure was unaffected. The results are in accordance with the hypothesis that inhibition of sensory perception by ketamine in subanesthetic concentrations is due to N-methyl-D-aspartate receptor blockade. It is suggested that N-methyl-D-aspartate receptor-mediated transmission is involved in the processing of sensory information in the human brain.

Adult↗
PubMed1991

A new version of the ischemic tourniquet pain test.

A new method of producing ischemic tourniquet pain is presented. The present test model showed a sex difference in the pain recordings. Sum pain intensity (SPI) for a 5 min trial period of ischemic pain was lower for males than for females (p less than 0.0001). The observed variability between male test subjects was greater than between female subjects, while the variation in pain scores within subjects was lower for males compared to females. The differences between sexes as a group with respect to variability of pain recordings were not statistically significant. Due to the observed sex differences in pain recording it is recommended to use test subjects of the same sex when restricting the test procedure to a limited number of subjects. The present version of the tourniquet pain test, used according to the recommended criteria, allows discriminating between i.v. administered placebo, opioid analgesics (pethidine) and ketamine.

Adult↗
PubMed1990

Evidence of a role for NMDA receptors in pain perception.

Both chiral forms of ketamine caused analgesia when administered in subanesthetic doses to human volunteers suffering acute, experimentally induced ischemic pain. S-Ketamine was 4 times more potent than R-ketamine as an analgesic agent in this model system. The relative order of analgesic potency of the two enantiomers was compared to their relative affinity for phencyclidine (PCP) binding sites (associated with the NMDA receptor-operated ion channel) and for sigma binding sites (which are not associated with the NMDA receptor complex). The relative analgesic potency of the enantiomers correlated positively with their relative affinity for PCP sites and negatively with their relative affinity for sigma sites. The results strongly indicate that PCP sites, but not sigma sites, are functional receptors mediating the analgesic effect of ketamine. This is consistent with the hypothesis that NMDA receptors are essential for pain perception in humans. Disturbances of other sensory modalities, in particular somatosensory perception, vision and hearing, were the main side-effects observed. These effects were qualitatively similar for both enantiomers and were closely associated with their analgesic action. The NMDA type of excitatory amino acid receptor thus appears to be widely involved in the processing of sensory afferent signals in the human brain.

Humans↗
PubMed1990

[Ketamine: clinically useful--pharmacologically interesting].

Ketamine has been employed as an anesthetic for 25 years. It is the only PCP-like dissociative anesthetic in clinical use. Favourable experience with ketamine in combat situations and at accidents, together with its ability to block the effect of the excitatory neurotransmitter glutamate on NMDA-receptor mediated neurotransmission, has attracted greater attention to this drug in recent years. The indications for and the use of ketamine as an anesthetic is described, and its various side-effects discussed. Combination with benzodiazepines greatly reduces these side-effects. Several pharmacological mechanisms may contribute to the effects of ketamine, in particular when large (anesthetic) doses are given. Recent investigations indicate that the analgesic and anesthetic effects as well as the "dissociative" phenomena seen after analgesic doses are due to PCP receptor mediated inhibition of excitatory amino acid transmission at NMDA synapses. The excitatory effect observed at higher doses, however, may be mediated by the haloperidol sensitive sigma-receptor. The enantiomers of ketamine (R- and S-ketamine) differ in pharmacological profile and may enable improvement of ketamine as a drug.

Analgesia↗
PubMed1982

Chlorpromazine inhibition of enterotoxin-induced fluid secretion and cAMP production in rat ileum.

A heat-labile enterotoxin prepared from E. coli (EcLT) increased fluid secretion and cAMP production by segments of rat ileum in vivo and in vitro. The effect of this toxin was compared to that of cholera toxin (VcLT). The increase of cAMP occurred more rapidly after EcLT than after VcLT indicating a difference in the kinetics of uptake or action of the two toxins. Chlorpromazine (CPZ) 5 mg/kg given by intramuscular injection 1 h before application of the toxins inhibited the increase in cAMP levels and the increase in fluid secretion in vivo. CPZ 10(-4) M given together with the toxins to intestinal loops in vitro inhibited the increase in cAMP levels and fluid secretion by this preparation. Scanning electron microscopy revealed that CPZ caused extensive shedding of the fluid-producing mucosal cells.

Animals↗
PubMed1982

Differences between alpha-adrenergic and beta-adrenergic inotropic effects in rat heart papillary muscles.

alpha-And beta-adrenergic inotropic effects have been shown to be qualitatively different. In order to further characterize these difference we compared the mechanical response to alpha- and beta-adrenoceptor stimulation, respectively, in electrically driven left ventricular papillary muscles from rat heart. The muscles were stimulated by either isoprenaline (Beta-adrenoceptor stimulation), phenylephrine in the presence of propranolol (alpha-adrenoceptor stimulation) or phenylephrine alone (combined alpha-and Beta-adrenoceptor stimulation). Isometric tension (T), rate of rise and decline of tension (first derivate=T') and rate of transition from tension rise to tension decline (negative part of second derivative=T') were recorded. These recordings disclosed qualitative differences between the alpha-and Beta-inotropic response both in dose-response and time course experiments. Maximal Beta-adrenoceptor stimulation caused a small increase in Tmax (18%), intermediate increases in T'max (45%) and T'min (68%) and considerable increase in T'min (145%) ("Beta-type" effect). Maximal alpha adrenoceptor stimulation increased all qualities by about the same degree (23-24% ("a-type" effect). While Beta-adrenoceptor stimulation gave a dose-dependent and pronounced increase in the ratio T"min/T'max (relaxation-onset index), alpha adrenoceptor stimulation decreased it to subcontrol values and phenylephrine alone gave a small dose-dependent increase at higher dose. The time course of the alpha-adrenoceptor stimulation was characterized by a transient decrease in all qualities followed by an increase which reached maximum at 4-5 min. Beta-Adrenoceptor stimulation gave a monophasic response which reached maximum after 1-2 min. Phenylephrine alone gave mainly an "a-type" effect although T"min increased significantly more in the absence than in the presence of propranolol and T"min/T'max showed a small increase which developed slowly. Thus Beta-adrenoceptor stimulation activated relaxation compared to contraction by a higher degree than did alpha-adrenoceptor stimulation. This probably reflects different mechanisms of action. While the alpha-effect may rely primarily on an increased calcium influx, the Beta-effect probably is the final result of several subcellular effects of cyclic AMP.

Animals↗
PubMed1981

Mechanical response of rat myocardium to dibutyryl cyclic AMP in relation to effects of alpha-and beta-adrenoceptor stimulators.

Dibutyryl cyclic AMP, and alpha- and beta-adrenoceptor stimulators are all able to elicit inotropic effects. alpha- and beta-Adrenoceptor stimulation are known to change each myocardial contraction-relaxation cycle differently. In order to elucidate the myocardial function of cyclic AMP the effects of dibutyryl cyclic AMP on the contraction-relaxation cycle of isolated rat heart papillary muscle were examined and compared to the effects of alpha-and beta-adrenoceptor stimulation, respectively. Dibutyryl cyclic AMP (in the presence of propranolol) increased developed tension (Tmax) by 18%, rate of tension rise (T'max) by 46%, rate of tension fall (T'min) by 62% and onset-rate of relaxation (T"min) by 136%. These changes in the contraction-relaxation cycle were strikingly similar to those produced by isoprenaline (beta-adrenoceptor stimulation). The response to dibutyryl cyclic AMP, however, developed much more slowly than did the response to isoprenaline. The latter effect was associated with cyclic AMP elevation in a way indicating a trigger function for cyclic AMP. The alpha-adrenoceptor stimulation (by phenylephrine combined with propranolol), however, increased measures both for contraction and for relaxation by about the same degree, and the effects occurred without changes of cyclic AMP contents. Phenylephrine alone (combined alpha-and beta-adrenoceptor stimulation) elicited a substantial cyclic AMP elevation but gave mechanical effects only slightly different from the pure alpha-adrenergic response. Thus cyclic AMP effects did not seem to be fully expressed in this case. As a whole, the results indicate that the effects of both dibutyryl cyclic AMP and of isoprenaline are mediated by the cyclic AMP-system while alpha-adrenoceptor stimulation involves other mechanisms.

Adrenergic alpha-Agonists↗
PubMed1980

Competitive blockade of alpha-adrenergic receptors in rat heart by prazosin.

Phenylephrine (PE) in presence of propranolol evokes an alpha-adrenergic inotropic response in rat heart. The time course of this response is characterized by a transient decrease in maximal developed tension (Tmax) to subcontrol levels (negative phase of the inotropic response) followed by an increase which reaches maximum after 4-5 min. (positive phase of the inotropic response). Prazosin (PRZ), a selective alpha 1-receptor blocker, inhibited preferentially the positive phase of the inotropic response and displaced the dose-response curve of PE to the right in nanomolar concentrations, indicating a competitive mechanism of inhibition. Phentolamine, a non-selective alpha-blocker, blocked both the negative and the positive phase of the inotropic response to about the same degree. PRZ appears to be a competitive alpha-adrenergic antagonist with high affinity in rat heart. Two populations of alpha-adrenergic receptors may be present: one stimulatory (alpha 1) and one inhibitory.

Adrenergic alpha-Antagonists↗
PubMed1980

A radioimmunoassay for cyclic AMP (cAMP) obtained by acetylation of both unlabeled and labeled (3H-cAMP) ligand, or of unlabeled ligand only.

A sensitive radioimmunoassay (limit of detection 7 +/- 1 fmol per tube) for cyclic AMP (cAMP) based on acetylation of both 3H-cAMP and unlabeled ligand was developed. Rabbit anti-cAMP antibodies had an apparent Ka for the acetylated ligand of 2 x 10(10) l/mol. When the unlabeled ligand only was acetylated an increased sensitivity was obtained without loss of specificity.

Acetylation↗
PubMed1978

Effect of prostaglandins and hormones on cyclic AMP formation in rat hepatomas and liver tissue.

The formation of cyclic AMP was studied in normal liver, subcutaneous hepatomas derived from MH1C1 cells, and premalignant liver and primary hepatomas induced by the carcinogens 2-acetylaminofluorene (AAF) and 4-dimethylamino-azobenzene (DAB). While only very slight effects of prostaglandins (PG) were seen in slices of normal liver, all the hepatomas responded strongly to PGE1 and PGE2. The hepatomas also had increase PGE1-sensitive adenylate-cyclase activity. PGF1alpha and PGF2alpha did not increase the cAMP level significantly either in the liver or in the hepatomas. During AAF carcinogenesis the response to PGE1 increased slightly during the carcinogen feeding, and was greatly elevated only in the fully developed hepatomas. This is in contrast to the increase in adrenalin response seen during carcinogenesis, which starts much earlier, and reaches a peak value within 8--10 weeks. It is concluded that various hepatomas have elevated responsiveness to PGE1 and PGE2 as well as to adrenalin, but the course of change in the tissues' ability to respond to these agents during carcinogenesis is very different.

Adenylyl Cyclases↗
PubMed1978

Qualitative differences between beta-adrenergic and alpha-adrenergic inotropic effects in rat heart muscle.

If beta- and alpha-adrenergic inotropic effects are cyclic AMP dependent and cyclic AMP independent, respectively, they may be qualitatively different. The inotropic effects of beta-receptor stimulation (isoprenaline) and alpha-receptor stimulation (phenylephrine combined with propranolol) were characterized in isolated perfused rat hearts, rat atria and rat papillary muscles. The beta-effect reached its maximum before the alpha-effect. The alpha-effect followed a three-phasic time-course indicating both stimulatory and inhibitory components. The aortic pressure wave (perfused heart) indicated a shorter contraction phase after beta-stimulation than after alpha-stimulation. The time to peak tension (atrium, papillary muscle) was relatively shorter after isoprenaline than after alpha-stimulation, which tended to prolong it. The contraction-relaxation cycles (atrium, papillary muscle) were examined by recording the isometric tension (T), its first (T') and second (T'') deri derivatives. alpha and beta-stimulation both increased Tmax, T'max (maximal rate of tension rise), T'min (maximal rate of tension decline) and T''min (maximal rate of transition from rise to decline of tension). Isoprenaline increased T'min (papillary muscle) and T''min (atrium, papillary muscle) relatively more than did alpha-stimulation, i.e. the relaxing processes were activated relatively more by beta-stimulation. The results indicate different mechanisms for the two adrenergic inotropic effects. The relatively larger activation of relaxation by beta-stimulation is assumed to be caused by clic AMP.

Adrenergic alpha-Agonists↗
PubMed1977

Increased level of cAMP in the rat intestinal mucosa caused by sodium lauryl sulphate.

The level of cyclic AMP in the jejunal mucosa from tied loops of anaesthetized rats was found to be significantly increased (27-50%) when sodium lauryl sulphate (SLS) was added to the loop fluid (2-27 mM). Imidazole (25 mM) did not significantly alter the resting level of cyclic AMP, but reduced the increase caused by SLS (17 mM). Theophylline (25 mM) significantly increased the intestinal level of cyclic AMP, and potentiated the increase caused by SLS. Ouabain (2.5 mM) did not alter the level of cyclic AMP in the presence or in the absence of SLS. The results of previous experiments on the increases in intestinal absorption caused by SLS or by dibutyryl cyclic AMP (Briseid et al., 1974, 1976) are discussed in light of the present data. It is concluded that the SLS-effect on absorption can only partly by ascribed to its effect on the intestinal level of cyclic AMP.

Animals↗
PubMed1976

Cyclic AMP formation and morphology of myocardial cells isolated from adult heart: effect of Ca2+ and Mg2+.

Adult rat heart cells were isolated by perfusion with a calcium-free phosphate buffer containing collagenase. Optimal conditions gave a high proportion of elongated cells. Isoprenaline increased cydic AMP content linearly, with ED50 (dose effective in 50% of the population) about 10(-7) M. Ca2+ made the cells spherical, and it nearly abolished cyclic AMP response as did lack of Mg2+.

Animals↗