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Biomedical subjects

K Nieber

Publications and source records attributed to K Nieber.

At least 55 records · Page 3Linked to original sources

Effects of substance P on isolated preparations from rabbit and rat renal arteries.

Substance P (SP) increased the tone of isolated ring preparations from renal and pulmonary arteries from rat but not from rabbit. Indomethacin decreased the amplitude of SP-evoked tone by 50%. SP inhibited in a dose-dependent manner the electrically-evoked contractions of the rabbit and rat renal arteries. The threshold concentrations producing inhibitory effects of SP were 10(-12) M for rabbit arteries and 10(-9) M for rat arteries. The maximal inhibition was observed at 10(-8) M and 10(-6) M, respectively. In the renal arteries of spontaneously hypertensive rats SP potentiated the electrically-evoked contractions. SP caused relaxation of the rabbit renal arteries, previously contracted with noradrenaline (10(-7) M), high [K+]0 (30 mM) and prostaglandin F2 alpha (10(-6) M). The results have shown that the effects of SP on the arterial contractions depend on the species and on the normal or pathologic conditions. A direct action of SP on the arterial muscle cells is suggested.

Animals↗

Effect of the N-terminal tetrapeptide of substance P SP (1-4) and tuftsin on the pre- and postsynaptic transmitter outflow in rat adrenal gland slices.

Two structurally related tetrapeptides, the N-terminal tetrapeptide of substance P SP(1-4) and tuftsin, exerted some similarities in modifying immune reactions and normalizing stress-induced disorders in the catecholamine system of adrenals. This paper presents results about the effects of tuftsin and SP(1-4) on the cholinergic-adrenergic interaction in rat adrenal gland slices. Both, tuftsin and SP(1-4) inhibited the nicotine-evoked [3H]noradrenaline outflow (postsynaptic effect), but the effect of SP(1-4) was more pronounced. SP(1-4) also inhibited the electrically stimulated [3H]ACh outflow (presynaptic effect), whereas tuftsin did not affect the ACh outflow. It is suggested that the regulation of the cholinergic-adrenergic interaction in adrenals is mediated by specific receptors, which are different on the pre- and postsynaptic side.

Acetylcholine↗

Long-term effects of substance P on the isolated guinea pig trachea.

The undecapeptide substance P(SP) and its C-terminal sequence SP-5-11 induced a dose-dependent contraction of the isolated guinea pig trachea. SP-5-11 had a more potent bronchoconstrictive action than SP-1-11. The distal part of the isolated guinea pig trachea showed a greater reagibility to SP-5-11 than the proximal one. There was a continuous increase of the amplitude of the SP-1-11-induced contractions when the neuropeptide was added several times at one-hour intervals. Incubation with 10(-6) M SP-1-11 for 5 h reduced the reagibility of the isolated guinea pig trachea to acetylcholine.

Animals↗

Responses of guinea-pig gastric, ileal and gall bladder smooth muscle to desamino-cholecystokinin-octapeptide (CCK 7).

Cholecystokinin 7 (CCK 7), a synthetic analogue of cholecystokinin/pancreozymin (CCK 33), increased in a dose-dependent manner the tone of the guinea-pig ileal, gastric and gall bladder smooth muscle preparations. In all these preparations CCK 7 was more potent than CCK 8 and CCK 33 and all three cholecystokinins were more potent than acetylcholine (ACH). Atropine and tetrodotoxin (TTX) did not influence the CCK 7 action in fundus and gall bladder muscle strips but reduced non-competitively its effect in ileal muscle strips. Neither GE 410 nor dbcGMP affected the ACH and histamine (His) response of the muscle strips but both antagonists shifted the dose-response curve of CCK 7 to the right, GE 410 (cholecystokinin antagonist) being a much more potent antagonist of CCK 7 as compared to dbcGMP. In all muscle strips a competitive action on the CCK 7 responses was found for GE 410. In gastric muscle strips a competitive influence on the CCK 7 responses was found for dbcGMP at low concentration (1 x 10(-5)M) and a non-competitive influence at high concentration (5 x 10(-4)M). The results suggest that the contractile effects of CCK 7 in the isolated ileal smooth muscle are realized by cholinergic and direct myogenic mechanisms, whereas in the isolated gall bladder and gastric smooth muscles, by a direct myogenic mechanism only.

Animals↗

[Cholecystokinin-peptides--new knowledge and possibilities for clinical use].

This issue comprises selected topics of CCK peptides. CCK peptides are linear peptides and were found within and outside the CNS. There is growing evidence that CCK peptides play a physiological role in food intake, contraction of gallbladder and regulation of motility of the gastrointestinal system. New aspects of the CCK research are concentrated on interaction with other transmitter systems especially with the dopamine and opioid system. The therapeutic action to improve clinical symptoms in human is unclear up to new. World-wide, the interest is focused to determine the potential of CCK peptides as an antipsychotic agent by controlled clinical studies.

Animals↗

Effect of substance P (SP) and the N-terminal SP-analogue SP (1-4) on the pre- and postsynaptic transmitter release in rat adrenal gland slices.

In the adrenal medulla ACh released from endings of splanchnic nerve stimulates catecholamine secretion by activation of nicotinic receptors localized on the chromaffin cells. Neuropeptides including SP may influence the catecholamine secretion. This report represents a study of the nature of the effect of SP and SP (1-4) on the cholinergic-adrenergic interaction in rat adrenal gland slices. In particular, the contributions of pre- and postsynaptic effects have been examined. The effect of SP and SP (1-4) on the electrically stimulated 3H-ACh outflow and on the nicotine-evoked 3H-noradrenaline (NA) outflow was determined. SP and SP (1-4) inhibited the evoked 3H-NA outflow in a dose-dependent manner. A dose-dependent inhibition by SP and SP (1-4) was also found in respect to the stimulated 3H-ACh outflow. Both substances had no effect on the basal 3H-transmitter outflow. SP had a stronger inhibitory effect on 3H-ACh outflow (ID50 = 1 X 10(-7) M) than on evoked 3H-NA outflow (ID50 = 8 X 10(-7) M). We discuss the functional role of SP to modulate the catecholamine secretion in adrenals especially in stressful situations as well as consequences with regard to the synthesis of selectively acting SP-analogues.

Acetylcholine↗

Influence of adrenal demedullation on stress-related behaviour in Wistar rats.

The influence of adrenal demedullation on stress-related behaviour (chronic immobilization) was investigated in respect to the following parameters and physiological processes: number of animals surviving the exposure, blood pressure behaviour, endogenous opioid system, pain sensitivity, endogenous level of substance P (SP) in pituitary and hypothalamus. The results showed that chronic immobilization stress and adrenal demedullation induce the same direction of alterations of physiological processes and parameters. This fact suggests the involvement of common regulatory mechanisms both in demedullation and chronic stress. An important process in this respect may be the induction of functional insufficiency of the adrenal medulla especially concerning the adrenal peptidergic mechanisms. Contrary to the sham operated rats the demedullated animals showed differences in their stress-related behaviour of parameters of adaptive regulatory processes. In rats with demedullation either no additional stress-related alterations of parameters in relation to the general adaptation processes were induced or the demedullation-induced alterations were antagonized partially or completely by chronic immobilization.

Adrenal Medulla↗

Relationship of substance P to catecholamines, stress, and hypertension.

This paper presents results on the function of the adrenal medulla, especially the influence of substance P (SP) on the cholinergic-adrenergic interaction. Interconnections between the function of SP and its role in the development and maintenance of hypertension as well as its role in stress and adaptation are investigated. Substance P acts only in situations with an increased nervous activity, for example, after stress-induced activation of the pituitary-adrenal and sympathetic-adrenal axis. Substance P normalizes stress-induced disorders by maintaining homeostasis in the catecholamine system. The basis of the antistress effect is the modulation of both biosynthesis and release of catecholamines in the adrenals. The homeostasis effect of SP, as well as the antistress effect do not require the complete sequence of the molecule. The N-terminal SP fragment is fully active and has no side effects.

Adrenal Glands↗

Suc-Tyr(SE)-Met-Gly-Trp-Met-Asp-beta-phenethylamide(410): a competitive antagonist of cholecystokinin-induced contractions in smooth muscles in vitro.

Suc-Tyr(SE)-Met-Gly-Trp-Met-Asp-beta-phenethylamide(410) has been studied for its ability to antagonize contractile responses of guinea pig gall bladder, ileum and stomach muscle strips to desamino-cholecystokinin-octapeptide (CCK-7) and cholecystokinin octapeptide (CCK-8). Both CCK-7 and CCK-8 at concentrations of 10(-11)M to 10(-7)M produced dose-dependent tonic contractions in all muscle strips. Suc-Tyr(SE)-Met-Gly-Trp-Met-Asp-beta-phenethylamide (10(-8)M-10(-5)M) inhibited reversibly in a dose-dependent manner the contractile responses to CCK-7 and CCK-8. At the same concentrations the antagonist shifted to the right in parallel to the dose-response curves for CCK-7 and CCK-8 without decreasing their maximum response. Analysis of the data after Schild gave pA2 values (410 potency as antagonist) of CCK-7 in gall bladder, ileum and stomach of 8.36; 8.0 and 7.56, respectively, and pA2 values of CCK-8 of 7.64; 8.94 and 8.52, respectively. The slope of the Schild plots for both CCKs did not differ significantly from the unity, which suggests that 410 is a competitive antagonist. The antagonistic action of 410 is reversible and appeared to be specific since at concentrations of 5 X 10(-6), it had no effect on contractile responses of the gall bladder, ileum and gastric muscle strips to acetylcholine or histamine.

Animals↗

[The role of the N-terminal of the substance P molecule in its action in stress-related behavioral and blood pressure disorders].

Substance P and the N-terminal sequences SP1-9, SP1-7, SP1-4 and SP1-2 were investigated in their action on stress related alterations in blood pressure behaviour, stress related disturbances in conditioned reflex learning behaviour, alterations in the endogenous opioid system and on the blood pressure behaviour of spontaneously hypertensive rats. In addition the occurrence of vegetative effects such as acute hypertension and histamine release from mast cells were investigated. The results of this work show that N- and C-terminal sequences of the Substance P molecule differ in their actions. Whereas the vegetative effects decrease if the SP molecule is shortened from the C to the N-terminus the "antistress effect" of the Substance P molecule remains unchanged. Whereas the N-terminal tetrapeptide SP1-4 can be considered "essential" for the "antistress effect", the C-terminal pentapeptide of SP is considered to be the "essential sequence" for the vegetative effects. These results will open new possibilities for the synthesis of selectively acting SP-agonists.

Animals↗

Effect of naloxone on the basal 3H-noradrenaline outflow from adrenal gland slices of normotensive and spontaneously hypertensive rats.

The adrenal medulla provides one of the most convenient preparations for studying the mechanism and control of neurosecretion. It has been suggested that neuropeptides including opioid peptides control the catecholamine secretion from adrenals and may play an important role in the maintenance of hypertension. In the present study the basal outflow of 3H-noradrenaline (3H-NA) from adrenal gland slices of normotensive and spontaneously hypertensive (SH) rats in the presence and without naloxone was examined. The amount of the basal 3H-NA outflow from adrenal gland slices of SH-rats was significantly higher compared with WKY-rats, whereas the outflow on slices of Wistar-rats was significantly lower compared with WKY-rats. Naloxone reduced the elevation of the basal 3H-NA outflow in a concentration-dependent manner, both in SH- and WKY-rats, but the absolute reduction was dependent from the level of elevation. These data suggest a functional interaction between opioid peptides and the basal catecholamine outflow during maintenance of hypertension.

Adrenal Glands↗

[Stress and the endogenous opioid system. III. Classification of the opioid system in the process of adaptation].

In this article the effects of stress-induced release of opioid peptides are integrated into the local (LAS) and general adaptation (GAS) syndrome. Findings are explained which plead for a participation in the LAS and AAS in the sense of a reserve mechanism for the maintenance of the homoeostasis. Three areas in which these opioid peptides possibly interact are discussed, articularly the adrenal glands because of their possible importance in effectuation of stress processes. Interactions between opioid system and catecholamines as well as of opioid peptides with substance P entitle to classify the opioid system as an effective regulator of biochemical processes in stress.

Acetylcholine↗

[Stress and the endogenous opioid system. II. Stress, stress models and endogenous opioid peptides].

Biochemical and pharmacological findings indicate an activation of the opioid system under certain stress influences. In this paper findings are discussed, according to which the activation of the opioid system depends on the temporary distribution pattern and the kind of the stressor. In response to stress opioid peptides are involved in excitatory and inhibitory processes. The participation of different types of opioids in central and peripheral stress-induced effects is discussed. Some findings suggest that beta-endorphin acts mainly centrally rather than peripherally, whereas the enkephalins take part in peripheral regulatory processes (gastrointestinal system, adrenal glands). Now there is evidence that the endogenous opioids modulate stress-induced effects, but there has been much controversy on how this fact should be established. These controversies mainly resulted from the many factors that influence activation.

Animals↗

[Stress and the endogenous opioid system. I. Physiology and pharmacology of opioid peptides].

In this article is given a survey on physiology and pharmacology of the opioid system. Opioid peptides are naturally occurring morphine-like acting metabolites of glycoprotein precursors. Of the opioid peptides proved hitherto in the organism met-, leu-enkephalin, dynorphin and beta-endorphin are characterized more in detail. Opioids react directly with opioid receptors. The opioid receptors are not a homogeneous system. Their distribution is depending on organs and species. Opioid peptides and receptors were proved within as well as outside the central nervous system. The main quantity of the endogenous beta-endorphin is stored in the pituitary gland. High concentrations of met-, leu-enkephalin and dynorphin are present in the gastrointestinal tract and in the adrenal glands. Opioid peptides are inactivated by enzymatic hydrolysis, in which case the splitting of the N-terminal tyrosine is decisive. The inactivation may be performed by amino peptidases, peptidyl dipeptide hydrolases or the angiotensin converting enzyme. The effect of the opioid peptides can be inhibited by opioid antagonists (naloxone, naloxazone). Up to now there are contradictory findings as to the presence of an endogenous opioid antagonist. In general, the presence of different opioid peptides and their different receptor preference indicate multiple functions in the organism. However, their physiological function is up to now only little clarified.

Adaptation, Physiological↗

Characterization of opioid dependence of isolated ileum of morphine dependent and of chronically stressed Wistar-Kyoto (WKY)-rats.

The opioid antagonist naloxone induced tonic contraction ("gut dependence") of isolated ilia of both morphine dependent WKY-rats and WKY-rats chronically stressed by immobilization. Morphine and met-enkephalin but neither dynorphine nor leu-enkephalin antagonized the naloxone induced "gut dependence" of isolated ilia obtained from morphine dependent WKY-rats. Met-enkephalin as well as dynorphine inhibited the "gut dependence" of chronically stressed rats; morphine and leu-enkephalin had no inhibitory effect. These differences between influences of different opioid peptides on "gut dependence" of morphine dependent rats versus "gut dependence" of rats chronically stressed by immobilization suggest that chronic stress induced or facilitated production of a different population of receptors.

Animals↗