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Biomedical subjects

P Oehme

Publications and source records attributed to P Oehme.

At least 19 recordsLinked to original sources

Functional studies with substance P analogues: effects of N-terminal, C-terminal, and C-terminus-extended analogues of substance P on nicotine-induced secretion and desensitization in cultured bovine adrenal chromaffin cells.

Substance P (SP) and SP analogues, including C-terminal, N-terminal, and C-terminus-extended analogues, have been investigated for their ability to modulate nicotine-induced secretion from bovine adrenal chromaffin cells in culture. Secretion was monitored by measuring the release of endogenous catecholamines by electrochemical detection following separation on HPLC and the release of endogenous ATP with an on-line luciferin-luciferase bioluminescence technique. SP is known to have the following two effects on nicotine-induced secretion of catecholamines (see Livett and Zhou, 1991): inhibition of the nicotinic response and protection against nicotinic desensitization. Secretion induced by 10(-5) M nicotine was inhibited 70-80% by SP, SP-methyl ester, and the C-terminus-extended analogue SP-Tyr12-NH2, 65% by (Ala3)SP-NH2, 45% by the C-terminal analogue SP(4-11), and 20 and 5% by the N-terminal analogues SP(1-7) and SP(1-5), respectively, when these peptides were present at 3 x 10(-5) M concentrations. The order of potency was SP = SP-methyl ester = SP-Tyr12-NH2 > (Ala3)SP-NH2 > SP(4-11) > SP(1-7) > SP(1-5). SP, SP-methyl ester, and (Ala3)SP-NH2 protected against nicotinic desensitization by 40-55%, and SP(4-11) protected by 20% (all at 3 x 10(-5) M). In contrast, the N-terminal analogues SP(1-7) and SP(1-5) and the C-terminus-extended analogue SP-Tyr12-NH2 at 3 x 10(-5) M did not protect against nicotinic desensitization. Cyclo-SP(3-9), Ac-SP(3-9)-NH2, SP(3-9), and SP(3-6) had neither inhibitory nor facilitatory effects on secretion.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate

In vivo-effect of intraadrenal nicotine and substance P application on rat adrenal medullary catecholamine secretion.

The present study was conducted to characterize in vivo the intraadrenal catecholamine (CA) secretion in rats. This was possible by using a microdialysis system (MDS) which mimics some properties of an artificial capillary. One end of this system was connected to a peristaltic pump, from the other end fractions were sampled at 5 min intervals. Concentrations of epinephrine (E) and norepinephrine (NE) in adrenal dialysate fractions were determined by HPLC electrochemical detection. Through this MDS nicotine was administered directly into the adrenal medulla of freely moving rats and the response of catecholamine release was determined. In the second part of the study the effect of exogenous substance P (SP) on spontaneous as well as on nicotine-stimulated CA release was investigated. Like nicotine, SP was administered directly into the adrenal medulla. At a flow rate of 25 microliter/min the transfer rates of CA and nicotine were approximately 1% whereas SP passed at a rate of 01.-0.2%. Under resting conditions CA release remained constant. In response to 2 x 10(-7) M nicotine (which resulted in local concentration of 2 x 10(-7) M), E and NE secretion increased 2.9 and 5.4-fold, respectively. However, due to an increased E response this difference attenuated with a later onset of the first stimulus. The higher concentrations of 10(-4) M resulted in 8.1 and 10.8-fold increases for E and NE. This latter response is clearly supraphysiologic and therefore the 2 x 10(-5) M concentration was used for further experimentation. CA secretion was stimulated with nicotine four times at 30 min intervals.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Glands

Substance P and beta-endorphin-like immunoreactivity in lavage fluids of subjects with and without allergic asthma.

Six atopic subjects with grass pollen allergy and six nonallergic healthy volunteers were enrolled into this study. Substance P-like immunoreactivity (SP-LIR) and beta-endorphin-like immunoreactivity (beta E-LIR) were determined in bronchoalveolar lavage (BAL) and nasal lavage (NAL) fluids before and after allergen (grass pollen) provocation. A significant increase in the baseline concentration of SP-LIR and beta E-LIR was seen in BAL of allergic subjects. In NAL of allergic subjects an increased baseline concentration of SP-LIR was found (beta E-LIR not detectable). After allergen provocation there was a rise of SP-LIR and beta E-LIR in BAL fluids of allergic subjects immediately after provocation. In NAL fluids of allergic subjects allergen challenge resulted in a rise of SP-LIR within 10 minutes. Allergen provocation did not influence SP-LIR and beta E-LIR concentration in BAL and NAL in nonallergic controls. The demonstrated higher baseline levels of SP-LIR and beta E-LIR as well as the increase after provocation in the BAL and NAL of allergic subjects but not in nonallergic controls support the hypothesis that these neuropeptides contribute to allergic reactions in airways of humans.

Adolescent

The possible role of substance P in the allergic reaction, based on two different provocation models.

It was shown in two different provocation models (nasal and bronchial provocation) that substance P (SP) may play an important role in the neurogenic inflammatory response in upper and lower airway disease. (1) Pretreatment with SP augments the antigen challenge response of the nasal mucosa. (2) The baseline bronchoalveolar lavage (BAL) concentrations of SP are elevated 8-fold in allergies (pollen asthma) as compared with normals, even outside of season. (3) The SP concentration in BAL increases significantly (p less than 0.05) after bronchial allergen provocation. These findings support a previous hypothesis of an abnormally elevated activity of nonadrenergic-noncholinergic excitatory nerves and are in accordance with the results of a decreased activity of neutral endopeptidase exaggerating neurogenic inflammatory responses in the airways, including bronchomotor tone hyperresponsiveness.

Adult

[Beta-endorphin and substance P in the perioperative period].

The modifying impact of anaesthesia on the stress reaction related to surgical trauma was investigated on the basis of the neuropeptidergic parameters of 66 patients who had to undergo a gynaecological radical operation. Anaesthesia was either performed as neuroleptanaesthesia or as epidural analgesia by using bupivacaine in combination with general anaesthesia. The plasma concentrations of substance P and beta-endorphin were taken as neuropeptidergic parameters. Both regulatory peptides show numerous corresponding synergisms. An acceleration of these neuropeptide systems is assumed to be present in severe disturbance of homeostasis. Plasma concentrations of substance P and beta-endorphin were examined at 11 measuring points in the perioperative and intraoperative periods. The plasma concentration of substance P significantly declines in the preoperative period while the concentration of beta-endorphin in the plasma remains at a relatively constant level. In the dynamics of beta-endorphin in the plasma significant differences between the two anaesthetic techniques become apparent in the intraoperative period. Those patients given epidural analgesia have a significantly higher maximum concentration at a later date. This difference is attributed to the possible loss of the adrenal medullary function due to partial sympathetic blocking. Single observations in patients pregnant in the last trimester testify to an extraordinary adaptability at the end of pregnancy.

Adult

Endogenous opioid dependence--a basic pathophysiological phenomenon of stress-induced and genetically fixed disturbances in adaptation--influence of substance P.

Disturbances in adaptive processes can be induced by chronic exposition to stress or can result from a genetical predisposition. Experimental data of chronically stressed Wistar rats and of spontaneously hypertensive rats (SHR) demonstrate a relation between a decreased level of substance P (SP) in adrenals, the existence of a dependence on endogenous opioid peptides and an increased regulatory level of blood pressure. The endogenous level of SP was determined by using a RIA. The dependence (physical) on endogenous opioid peptides was detected by using the method of "gut dependence". SP injection i.p. once a day for 4 d antagonized the dependence on endogenous opioid peptides and normalized the increased level of blood pressure in both animal models. Investigations on SHR had shown that the adaptive effect of SP on blood pressure and endogenous opioid dependence is bound to the premise of an acute stimulated endogenous opioid system at the moment of SP-application. Experimental findings suggest that different systems of opioid peptides take part in the etiopathogenesis of genetically predisposed hypertension of SHR and in stress-induced increase of blood pressure level of Wistar rats. The effect of SP on blood pressure and endogenous opioid dependence will be discussed as a result of the modulatory influence on the cholinergic-opioid-peptidergic interaction.

Adaptation, Physiological

Influence of capsaicin on the reagibility of the isolated guinea pig trachea.

Capsaicin induced a concentration dependent contraction of isolated guinea pig tracheal spirals but did not reduce the tone of submaximally precontracted preparations neither per se nor after pretreatment with a tachykinin antagonist. The contractile reactions to capsaicin did not differ significantly between tracheal preparations obtained from sensitized and nonsensitized animals. A single application of capsaicin (10(-5) M for 15 min) induced a strong contraction of the preparations followed by complete tachyphylaxis to further applications of capsaicin. Such pretreatment with capsaicin did not influence the reagibility of isolated guinea pig tracheas to acetylcholine added exogenously but reduced the allergic contractions of preparations obtained from actively sensitized animals significantly. It is suggested that neuropeptides (e.g. substance P) might be involved in the allergic bronchoconstriction in vitro.

Animals

Possible role of substance P on regulation of pituitary-adrenal axis.

The effects of chronic immobilization stress on the physiological responses of male rats were studied. The results indicate that the SP-like immunoreactivity (SPLIR) is diminished in the adrenals and pituitary after chronic stress. In vitro noradrenaline (NA) release from adrenals was increased. The i.p. administration of SP during the stress procedure normalized the increased NA release in vitro indicating that the catecholamine secretion may be influenced by SP. On the other hand, in demedullated animals the SPLIR in the pituitary was partly reduced and the blood pressure was increased. In such animals chronic stress resulted in an increase of SPLIR in the pituitary in comparison with nonstressed, demedullated animals, but was without effect on the blood pressure. It is concluded that exposure to SP and the resulting decrease of noradrenaline release may have a significant influence on the pituitary-adrenal responsiveness to stress.

Adrenal Glands

Substance P, mean apnoea duration and the sudden infant death syndrome (SIDS).

In order to evaluate disturbances of the respiratory control in the first year of life in children with a statistically enhanced risk of SIDS, substance P-like immunoreactivity (SPLI) in plasma and mean apnoea duration (MA) were examined. 4 groups of infants were investigated: Controls, full-term infants with anamnestic SIDS-risk factors, preterm infants with additional risk factors and preterm infants without such factors. Infants aged from -4(corrected age) to 63 weeks. SPLI in plasma was determined by a specific, homologous radioimmunoassay. The SPLI-level was significantly higher in controls (n = 41; means +/- SE = 36.37 +/- 4.86 pg/ml) than in preterm infants without (n = 21; 25.41 +/- 5.54 pg/ml) or with additional anamnestic risk factors (n = 111; 25.89 +/- 3.09 pg/ml). SPLI was higher in full-term SIDS-risk infants (n = 150; 30.73 +/- 2.35 pg/ml) than in the preterm groups. There is a significant age dependence in the groups full-term SIDS-risk infants and preterm infants with additional risk factors. During maturation the SPLI-level in plasma rises in these groups from lower values. The MA-values were determined by means of a daytime polygraphy. There is an age dependence of the MA-values during active sleep in full-term SIDS-risk infants and in preterm infants with additional anamnestic risk factors. In the age group 4-17 weeks (peak of SIDS frequency) in active sleep the MA-values were significantly higher in all 3 risk groups than in the controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Humans

Stress-induced dependence on endogenous opioid peptides--a fundamental process in the pathophysiology of a disturbed adaptation--its influence by substance P.

Using previous findings of stress-induced disturbances in regulation of peripheral and central function within the general adaptation process and hints from the literature to a multiple participation of opioid peptides in adaptive processes, this paper represents experimental data which gives hints to a functional relation in the etiopathophysiology between the development of stress-induced dependence on endogenous opioid peptides and stress-induced disturbances in blood pressure regulation and to the adaptive effect of substance P within the peptidergic interaction with endogenous opioid peptides and its importance for the physiology or pathophysiology of adaptive processes.

Animals

[Effect of the N-terminal fragment of substance P1-4 on the somatic manifestations of the stress reaction and on the catecholamine content of the adrenals in rats].

The antistress affect of the substance P1-4 N-terminal fragment (ARG-Pro-Lys-Pro, 100 mkg/kg, i.p.) has been studied on the model of immobilization stress in rats. It was ascertained that the preparation of protective effect is revealed to the greatest extent on the exhaustion stage (48 h of immobilization), which served to prevent the lymphoid organs mass reduction and ulcer development and also accounted for greater adrenaline and noradrenaline content preservation in tissues and chromaffin cells of adrenal glands in stressed animals.

Adrenal Glands

Influence of substance P and substance P--sequences on immunocompetent cells.

The influence of substance P (SP) and substance P-sequences on spleen cell cultures of mice and on rat lymph node mononuclear cells was studied. SP and the N-terminal fragments SP(1-4) and SP(1-7) were capable of inducing the secretion of lymphokines with chemotactic properties for polymorphonuclear leukocytes and lymphocytes. The peak of the dose-response curves appeared in a concentration range of 10(-11) to 10(-10) mol/l. The predominant migratory stimulatory activity was found at a molecular mass of 12,000 and 23,000 dalton and an inhibitory activity at 35,000 dalton. The C-terminal part of the peptide, SP(6-11), SP(7-11), SP(8-11), SP(9-11), was not able to induce such lymphokine secretion. The experimental results display the importance of the N-terminal fragment for the lymphokine secretion, and support the hypothesis that SP is also a peptide with modulatory functions in the immune response.

Animals

[The role of substance P in regulating bronchomotor tone and the pathogenesis of bronchial hyperreactivity].

Substance P (SP) is localized in sensory nerves of the respiratory tract in close connection to the effector cells of inflammatory and allergic bronchial diseases. SP is proposed to play an important role in the pathogenesis of bronchial asthma because of its ability to induce bronchoconstriction, vasodilatation and an edema of the mucous membrane and to enhance the secretion of tracheobronchial glands. Furthermore inflammatory and immune cells are influenced by SP. SP seems to have a complex action in the regulation of the bronchial tonus. Especially differences in the action of partial sequences of the peptide may be important in the pathogenesis of asthma.

Animals

Relationship between neuropeptides and gastrointestinal smooth muscle activity.

The actions of substance P (SP) and met-enkephalin (ME) on the motility of stomach and small intestine were compared in conscious dogs. In stomach the two peptides induced different effects on the motility whereas in small intestine SP and ME caused similar actions. The effects of SP were not influenced significantly by ME or naloxone applied before. Furthermore, SP desensitization did not influence the typical response to ME. Our results indicate no interactions between SP and ME in modulation of gastrointestinal motility. The presence of two peptidergic systems existing independently is discussed.

Animals

[Characteristics of the course of the wound process in spontaneously hypertensive rats and the effect of morphine, substance P and its fragment SP1-4].

The paper demonstrates that in spontaneously hypertensive rats (SHR) as compared with normotensive controls exudative processes at the sites of lesions are much more prominent. Such exudative processes include edema, fibrinous exudation as well as permeability of capillaries and venular walls for leukocytes. These effects prolong the phase of its inflammation and retard the regeneration phase in wound healing. Morphine and SP1-11 stimulate in a similar fashion repair during wound healing in the both rat strains. Their effect is similar to the effect of opioid peptides. SP1-4 does not affect vessel reactivity and wound healing in SHR, which is related to disturbed expression of receptors to SP fragments. Synergism in the effect of two functional antagonists i.e. opioids and SP on wound healing confirms our hypothesis about the role of pain as an inducer of a variety of mechanisms underlying repair regeneration.

Animals