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Biomedical subjects

M Pokorski

Publications and source records attributed to M Pokorski.

At least 37 records · Page 2Linked to original sources
PubMed2000

Classical protein kinase C and its hypoxic stimulus-induced translocation in the cat and rat carotid body.

The presence, subcellular distribution, species specificity and possible hypoxic stimulus-induced translocation of classical protein kinase C (cPKC) isozymes were examined in the carotid body. Carotid bodies were dissected from cats exposed in vivo to normoxic or acute hypoxic conditions and from normoxic rats. For immunohistochemistry isoform-specific monoclonal antisera to PKCalpha, PKCbetaI, PKCbetaII and PKCgamma were used. The immunoreactivity was visualized by fluorescein isothiocyanate (FITC) labelling. FITC/Texas red double-labelled specimens for the cPKC isozymes/tyrosine hydroxylase were used to demonstrate the chemoreceptor cell localization of cPKC isozymes. The immunofluorescence was detected using laser scanning confocal image technology. The results showed expression of the PKCalpha and PKCgamma but not PKCbeta isoforms in the cytoplasm of carotid body chemoreceptor cells. The double labelling provided evidence for the chemoreceptor cell localization of the cPKC isoforms detected. The immunostaining was most intense in the periphery of the perikarya, the nuclear envelope and, occasionally, the nucleoplasm. No major differences were found in the immunolocalization of PKCalpha and PKCgamma under normoxic and hypoxic conditions or between species. However, the immunoreactivity tended to accumulate more in the peripheral cytoplasm and away from the nucleus in the hypoxic chemoreceptor cell. This study demonstrates the presence of classical protein kinase C enzymes in chemoreceptor cells. The intensity of the immunoreactivity may suggest a role for the classical protein kinase C signalling pathway in shaping the hypoxic response at the carotid body. However, this study failed to provide firm evidence of this.

Animals↗
PubMed2000

Nocturnal oxygen enrichment in sleep apnoea.

We hypothesized that a modest oxygen enrichment, rather than 100% oxygen supplementation as used in previous trials, could result in improvement in ventilatory and cardiac symptoms, in patients with obstructive sleep apnoea (OSA), without jeopardizing the chemostimulant ventilatory drive. This hypothesis was tested in five male patients with OSA in a single-blinded trial consisting of one night spent sleeping in control room air (control night), followed by one night spent sleeping while exposed to air with a 9% enriched oxygen content (oxygen-enriched night). Oxygen enrichment resulted in a significant shift in the oxygen saturation profile towards values of > or = 95% and to decrease desaturation dips throughout the night. The apnoea index decreased from the control night to the oxygen-enriched night from 52.7 +/- 10.4 to 38.9 +/- 9.3; the decrease being greatest for the longest apnoeas (> or = 30 s). Additionally, the cardiovascular status improved. No signs of depressed chemostimulant drive in the oxygen-enriched night were detected. We conclude that nocturnal oxygen enrichment merits consideration for therapeutic trial in the prevention of long apnoeic and desaturation episodes.

Adult↗
PubMed1999

Protein kinase C--a potential modifier of carotid body function.

This article deals with the potential role of protein kinase C (PKC) in signal transduction in the carotid body. The carotid body is a chemosensory organ which, by sensing reductions in arterial blood oxygen tension, is primarily responsible for the hyperventilation of hypoxia. The mechanisms of transduction of the hypoxic stimulus into a neural signal regulating respiration are not clear. Hypoxia increases the phosphoinositide-specific phospholipase C (PLC) activity in the carotid body. The PLC-derived signalling molecules are known to activate PKC. The enzyme might, thus, have the potential to interact with the process of chemoreception. This article demonstrates that PKC is present in the chemoreceptor cells of the cat carotid body and discusses the biology of the enzyme relevant to chemosensory function. This gives rise to the hypothesis that PKC-mediated mechanisms alter chemoreceptor cell function to a sufficient extent to metamorphose the hypoxic signal into an increased discharge frequency in the apposed sinus nerve endings.

Animals↗
PubMed1998

Fatty acid acylation of dopamine in the carotid body.

In this article, we put forward a hypothesis concerning the assembling and storage of dopamine molecules in the dense-core vesicles of the carotid body chemoreceptor cell. We posit that dopamine molecules are packed and sustained in the vesicular form due to the formation of N-acyldopamine, a condensation product of fatty acid acyl chain and dopamine at the amino group of the latter. N-acyldopamine would then be stored in a micelle-like supramolecular structure formed due to self-association through the hydrophilic dopamine headgroups. This hypothesis may help explain the perennial problem of the role of dopamine in chemoception. It also draws attention to the possibility of the existence of neurotransmitters in the N-acylated form. This could lead to the design of acylated compounds that would play a role of prodrugs slow-releasing active substances by hydrolysis into the desired environment.

Acylation↗
PubMed1997

Hypoxia depletes ascorbate in the cat carotid body.

Vitamin C or L-ascorbate is an effective endogenous reducing agent influencing the functions that are involved with the redox mechanism. Detection of oxygen tension changes by the carotid body chemoreceptors is one such function. In this study we investigated the hypothesis that the level of ascorbate, if present, could change in the carotid body as a result of ascorbate's interaction in the chemosensing process, which would be reflected in the production of the ascorbyl radical. We addressed this issue by examining changes of the ascorbyl radical, using the in vitro electron spin resonance spectroscopy (ESR), in the carotid bodies dissected from pentobarbitone anesthetized cats exposed in vivo to three eucapnic, breathing gas mixtures of different O2 concentration: normoxic, 21% O2; hypoxic, 7% O2; and hypoxic-reoxygenated, 7% O2 followed by 100% O2. Each group consisted of five cats, yielding five pairs of carotid bodies for the ESR signal recording. We found that the intensity of ESR signals, measured as peak-to-peak amplitude, was diminished by 39 and 43% in the hypoxic and hypoxic-reoxygenated groups, respectively, compared with that in normoxia. The study shows that ascorbate was present in the normoxic carotid body and was depleted by hypoxia. We conclude that ascorbate is part of free radical mechanisms operative in the carotid body in hypoxia.

Animals↗
PubMed1997

Involvement of the motor trigeminal nucleus in respiratory phase-switching in the cat.

We investigated the hypothesis that the motor trigeminal nucleus, consisting of expiratory motoneurons, might be influential in termination of inspiration. We addressed the issue by comparing the effects on neural respiration of a reversible, unilateral, pharmacologic blockade of the motor trigeminal nucleus (5M), the medial parabrachial nucleus (PB), and of other nearby structures that are neutral for respiration in anesthetized, vagotomized, paralyzed, and ventilated cats. The blockade was achieved by microinjections of 2% xylocaine, laced with Pontamine Sky Blue to identify sites of injections, from the tip of a penetrating microelectrode. Integrated phrenic neurograms were recorded to quantify the time of neural inspiration (TI), expiration (TE), and the peak phrenic amplitude. We found that blockade of the 5M caused a pattern of apneustic respiration, consisting of a selective prolongation of inspiratory phases that were interrupted by short expiratory pauses. In contrast, blockade of the PB resulted in a prolongation of both TI and TE, which corresponds to a mere slowing of respiration. The results confirmed important functions of the rostral pons in ventilatory control but pointed to the 5M rather than PB as a structure underlying the inspiratory off-switch. We conclude that the motor trigeminal nucleus may have a part in the pontine pneumotaxic mechanism.

Animals↗
PubMed1997

ATP activates phospholipase C in the cat carotid body in vitro.

In this study we investigated the hypothesis that ATP could play a role in the transduction of the hypoxic stimulus in the carotid body (CB) by being a regulator of the phosphatidylinositol-4,5-bisphosphate (PIP2)-specific phospholipase C (PLC). We addressed this question by comparing the PLC activity in the absence and presence of ATP in homogenates of CBs dissected from anesthetized cats that were preexposed in vivo to the contrasting conditions of normoxia (PaO2 approximately 90 mmHg) and hypoxia (PaO2 approximately 20 mmHg). The tissue of a nearby superior cervical ganglion (SCG) was used as a reference. The homogenate was the source of PLC. PLC activity was assayed by measuring the formation of radioactive inositol 1,4,5-trisphosphate from [3H]PIP2, used as an exogenous substrate. ATP was added to the assay mixture at the concentrations of 0.25 mM and 1 mM, chosen on the basis of test trials on ATP dependence of PLC changes. We found that ATP increased appreciably the PLC activity over its basal (absence of ATP) level in the normoxic carotid body. The stimulatory effect of ATP was augmented in the hypoxic carotid body, the lower ATP concentration having a stronger effect. Such PLC changes were absent in the SCG. These findings suggest a regulatory role for ATP in the PLC-linked hypoxic signal transduction in the carotid body.

Adenosine Triphosphate↗
PubMed1997

[Diaphragmatic electromyogram and respiratory pattern after unilateral and bilateral partial denervation of the diaphragm in the cat].

In the present study we investigated the mechanism of early respiratory compensation of partial paralysis of the sternal and lateral diaphragm due to an unilateral or bilateral section of the C5 rootlet of the phrenic nerves in anesthetized cats. Compensatory effects were evaluated from the recordings of the bilateral diaphragmatic EMGs, neural respiratory pattern and ventilation. The results of the study demonstrate that successive C5 denervation of the diaphragm caused a decrease in the ipsilateral diaphragmatic EMG. Bilateral C5 section evoked an up to 10 percent decrease in minute ventilation. The compensation of the unilateral and then bilateral partial impairment of the muscle function was achieved always by an increase in the neuromuscular projection to the currently contralateral diaphragm. Neural mechanisms of compensation involve a general increase in the respiratory drive, expressed mostly as an increase in the frequency of breathing. The contribution of afferent respiratory muscles to these mechanisms is likely.

Animals↗
PubMed1997

Ultrastructural manifestation of pharmacologic inhibition of the activities of lipases and proteases in the cat carotid body.

This study is based on the premise that if a subcellular element of an organ performs an appreciable functional role, then its inhibition could influence the ultrastructural organization of the organ. We addressed this issue in the investigation on the carotid body, a chemosensory organ, by comparing the ultrastructure of its parenchyma in phenylmethylsulfonyl fluoride (PMSF)-injected cat with that of the normal cat. PMSF, an inhibitor of lipases and proteases, induced degenerative changes chiefly in subcellular components other than the neurosecretory and synaptic elements being associated with signal transduction. The study suggests that the inhibited enzymes might also have to do with the carotid body function.

Animals↗
PubMed1994

Endogenous benzodiazepine system and regulation of respiration in the cat.

Benzodiazepines, a class of drugs widely used as anxiolytics, can induce a depression of respiration. This study was designed to determine if endogenous benzodiazepine ligands could act in a similar fashion and exert a tonic inhibitory influence on respiration. Administration of a benzodiazepine antagonist should then facilitate respiration. This might be especially visible in hypoxia, the condition characterized by both central respiratory depression and potentially enhanced benzodiazepine expression. We addressed this issue by comparing the effects on the phrenic neurogram of the specific benzodiazepine antagonist flumazenil (200 micrograms i.v. boluses) in the contrasting conditions of hypoxia and hyperoxia in anesthetized, both spontaneously breathing and paralyzed ventilated cats. Contrary to our hypothesis, flumazenil showed a modest but definite inhibitory effect on respiration. Flumazenil also lengthened the duration of the Hering-Breuer inspiratory inhibition. The respiratory depression was neither related to chemical drive nor to the GABA receptor complex, for it was sustained after antagonism of GABA with picrotoxin and bicuculline. We conclude that the endogenous benzodiazepine system is unlikely to play an inhibitory role in the regulation of respiration. The physiologic role of this system remains to be established.

Animals↗