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Biomedical subjects

W Kromer

Publications and source records attributed to W Kromer.

At least 55 records · Page 3Linked to original sources

Differential effects of SKF 10,047 (N-allyl-normetazocine) on peristalsis and longitudinal muscle contractions of the isolated guinea-pig ileum.

The purpose of this study was to investigate the differential involvement of distinct types of opioid receptors in the modulation of intestinal peristalsis compared to electrically induced longitudinal muscle contractions. Like naloxone, the proposed sigma-agonist and mu-antagonist SKF 10,047 (N-allyl-normetazocine) dose-dependently enhanced peristaltic circular muscle contractions in the isolated guinea-pig ileum. Pre-application of SKF 10,047 at a concentration which itself enhanced peristalsis by 20% on average strongly attenuated the inhibition of peristalsis produced by opioids previously proposed to act via mu-opioid-receptors in the guinea-pig ileum, i.e. normorphine, beta-endorphin, D-Ala2-D-Leu5-enkephalin and d-Ser2-L-Leu5-enkephalyl-Thr, but less strongly attenuated the inhibition produced by compounds suggested to act via kappa-opioid-receptors in this tissue, i.e. ethylketazocine and dynorphin (1-13). In contrast to its effect on peristalsis, SKF 10,047 inhibited the electrically induced contractions of the myenteric plexus-longitudinal muscle preparation in a naloxone-reversible fashion. It may be concluded that mu-and kappa-opioid receptors are of a greater functional significance than sigma-receptors in the control of peristalsis. sigma-Receptors might participate predominantly in modulating the release of acetylcholine which underlies the electrically induced longitudinal muscle contraction.

Animals↗

Opiate tolerance/dependence in the isolated guinea pig ileum is associated with an increased sensitivity to acetylcholine.

The number of rhythmic circular muscle contractions elicited by acetylcholine was increased in isolated intestinal segments taken from morphine-tolerant/dependent guinea pigs and exposed in vitro to an adequate normorphine concentration. Segments which underwent a partial withdrawal in vitro showed some degree of supersensitivity to acetylcholine which was, however, not significant. In contrast, basal peristaltic reflex activity was enhanced during a partial opiate withdrawal but not during exposure of the segments to a normorphine concentration high enough to maintain opiate tolerance/dependence. These data suggest that a supersensitivity to acetylcholine participates, at least partially, in the development of tolerance to the inhibitory action of opioids upon intestinal peristalsis.

Acetylcholine↗

Opioids modulate intestinal peristalsis at a site of action additional to that modulating acetylcholine release.

The nature of the interaction between cholinergic and opioid mechanisms controlling peristalsis in the intact segment of the guinea-pig ileum was examined. The induction of rhythmic peristaltic activity by acetylcholine was dose dependently inhibited and facilitated by preapplication of, respectively, normorphine and naloxone. The action of intestinal opioids occurs, at least partially, at a site of action differing from that modulating the release of acetylcholine from the myenteric plexus. Interruption of the peristaltic reflex by hexamethonium, atropine, tetrodotoxin or desensitization of the segments to serotonin also strongly impaired or abolished the initiation of circular muscle contractions produced by naloxone. Therefore, no indication could be found for a direct action of naloxone upon the circular muscle. Rather, intestinal opioids appear to be involved in regulating the activity of the reflex arc.

Acetylcholine↗

Release of immunoreactive-dynorphin from the isolated guinea-pig small intestine is reduced during peristaltic activity.

The guinea-pig small intestine contains high amounts of immunoreactive dynorphin (9 pmol/g), which is released from the in vitro preparation under resting conditions (basal release). Initiation of peristaltic activity by distension of the intestinal wall via sustained elevated intraluminal pressure lowers the levels of immunoreactive dynorphin in the bathing solution (by more than 60%). The present data are suggestive of a role of this endogenous opioid peptide in the control of intestinal peristalsis.

Animals↗

Regional distribution of an opioid mechanism in the guinea-pig isolated intestine.

Opioid receptor blockade by naloxone enhanced peristalsis in isolated segments from the guinea-pig duodenum, jejunum and ileum, increasingly aborally. Thus, an increase in the influence of an intrinsic opioid mechanism may be responsible for decrease in the level of peristaltic activity, observed aborally. However, the peristalsis of ileal segments which worked against their closed distal end was enhanced by naloxone to a similar degree as normal peristalsis.

Animals↗

Dual action of somatostatin upon peristalsis in the guinea pig isolated ileum.

Peristalsis in the guinea pig isolated ileum usually consists of alternating periods of activity and peristalsis-free intervals (PFIs). When PFIs were shorter than, on an average, 5 min, somatostatin at 10(-9) or 10(-8) M prolonged subsequent PFIs. By contrast, when PFIs were longer than 5 min. somatostatin shortened subsequent PFIs. No evidence could be found for an interaction of somatostatin with opioid mechanisms. The present work demonstrates that the action of a substance upon intestinal peristalsis in vitro may depend, at least in the case of somatostatin, upon the functional state of the isolated intestinal segment.

Animals↗

Naltrexone influence on hibernation.

In the garden dormouse, opiate receptor blockade by naltrexone decreased the score for sleeping behaviour during hibernation at 24.00 h, indicative of a possible involvement of endorphins in the control of hibernation.

Acclimatization↗

Mouse-killing in rats induces a naloxone-blockable increase in nociceptive threshold.

Mouse-killing behaviour in rats increased the nociceptive threshold for paw licking, as measured in the hot-plate test. This effect was prevented by the opiate antagonist naloxone, which, on the other hand, had no influence on mouse-killing behavior per se. It is concluded that opioid mechanisms may be involved in changes of nociceptive threshold associated with aggressive behavior.

Aggression↗

Peristalsis in the isolated guinea-pig ileum during opiate withdrawal.

Naloxone enhances peristalsis in isolated intestinal segments from morphine-dependent guinea-pigs to a greater degree than in naive preparations. These data suggest that a peripheral mechanism may be involved in the expression of opiate withdrawal in the small intestine, and indicate that the action of this mechanism leads, at least in vitro, to an increase in the number of peristaltic waves.

Animals↗

[Endorphins--endogenous peptides with morphine-like effects. 2. Biological importance, clinical apsects].

Since 1974 peptides with opiate-like action both in vivo and in vitro have been isolated from the nervous system of various vertebrates and man. The localization of these peptides (endorphins) within the central and peripheral nervous system reflects the possible biological functions in which they may participate: the response of the CNS to painful stimuli (dorsal horn of the spinal cord, central grey matter, thalamus); the control of emotions (limbic system); the regulation of vegetative functions (medulla oblongata); the response of the body to stress the control of endocrine function (hypothalamus, infundibulum, hypophysis); the control of extrapyramidal motor activity (brain stem) or the control of intestinal motility (intramural nervous plexus). Up-to-date knowledge suggests that the endorphins may function as neurotransmitters, neuromodulators or hormones and that such functions vary according to the special sites of synthesis, storage and action of these various peptides within the body.

Behavior↗

Porcine pituitary peptides with opiate-like activity: partial purification and effects in the rat after intraventricular injection.

A peptide material with opiate-like activity in the guinea-pig ileum was extracted from porcine pituitaries using a hot glacial acetic acid extraction method and was partially purified by gel filtration. When injected intraventricularly in rats, these purified peptides induced strong analgesia, catelepsy, respiratory depression and other opiate-like effects, which lasted for several hours.

Analgesia↗

[Continuing registration of muscle temperature during electromyography].

Measurements of muscle temperature were performed during and after contractions of human skeletal muscle using an electromyography-needle-electrode, which contains a thermo-element. The investigations aimed at explaining a drop in temperature during contraction, earlier described, and getting some aspects of possible employment of temperature measurements carried out simultaneously with electromyography. 1. The course of temperature during contraction (increase or decrease) depends on the heat of contraction, blood flow through muscle, penetration depth of the thermoelement, gradient of temperature and efficacy of a compression of blood vessels. It results from a superimposition of the single effects. 2. A decrease in temperature in various extremity muscles during contraction is explained by a compression of blood vessles caused by the shortening of muscle, as described earlier by other authors. 3. The interpretation of temperature curves, especially the quantitative interpretation, becomes very uncertain because of various sources of error. A differentiation between muscle heat and influence of blood flow is not sufficiently possible. 4. Nevertheless measurements carried out under conditions of disturbed blood supply, myopathies and polyneuropathies consistent with experiments performed during cooling and warming muscle in a water-bath, causing a reactive hyperemia or a defective circulation by using a blood pressure instrument show that changes in blood circulation are expressed by changes in temperature curves. Measurements carried out simultaneously on agonists and antagonists show satisfactorily the contrary changes in blood circulation known from the literature.

Adult↗