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Biomedical subjects

F Lembeck

Publications and source records attributed to F Lembeck.

At least 73 records · Page 4Linked to original sources
PubMed1987

Contractile effects of substance P and neurokinin A on the rat stomach in vivo and in vitro.

Substance P and neurokinin A (substance K) were infused into the coeliac artery of anaesthetized rats at doses of 0.06-20 nmol min-1. Both tachykinins caused contractions of the stomach, the threshold dose of neurokinin A being 10 times lower than of substance P. The dose-response curve for substance P was flatter than that for neurokinin A. On circular muscle strips from the rat gastric corpus in vitro, the dose-response curves for both tachykinins were parallel, neurokinin A being 10 times more potent than substance P. The contractions in response to 10 microM neurokinin A and to 30 microM substance P were 58 and 54%, respectively, of the maximal contraction to bethanechol (1 mM). The effect of substance P was reduced by atropine both in vivo and in vitro. In vitro, the contractions to substance P were also reduced by tetrodotoxin but left unaffected by methysergide. The action of neurokinin A was not affected by these drugs. It is concluded that neurokinin A contracts rat stomach by a direct action on the circular smooth muscle, whereas the action of substance P is mediated, at least in part, by cholinergic interneurones.

Animals↗
PubMed1986

Capsaicin sensitive afferent neurons from peripheral glucose receptors mediate the insulin-induced increase in adrenaline secretion.

The effect of insulin and of 2-deoxy-D-glucose (2-DG) on adrenaline secretion was compared in rats pretreated as neonates with capsaicin and in rats pretreated with the drug-vehicle. Capsaicin-pretreatment did not inhibit the fall in blood glucose concentrations induced by insulin or by fasting, nor did it affect the increase in blood glucose concentrations in response to 2-DG or restraint stress. Capsaicin greatly reduced the rise in urinary adrenaline excretion over 24 h and the fall in the adrenaline content of the adrenal glands normally induced by insulin. In contrast, capsaicin-pretreatment did not interfere with the rise in the adrenaline excretion and the fall in the adrenaline content of the adrenal glands normally induced by 2-DG. Insulin-induced hypoglycaemia as well as intracellular glucopenia in the brain caused by 2-DG activate hypothalamic centres which stimulate the nervous input to the adrenal medulla and adrenaline secretion. The fact that capsaicin interfered only with the adrenal effect of insulin suggests the involvement of afferent C-fibres in this insulin effect. Injection into the hepatic portal vein of a C-fibre stimulating dose of capsaicin increased arterial glucose concentrations in vehicle-pretreated rats but not in capsaicin-pretreated rats. The response was significantly diminished after bilateral vagotomy. From the present results it is concluded that glucose receptors in the hepatic portal vein transmit signals via afferent, capsaicin sensitive C-fibres to the brain and that activation of this pathway is essential for the increase in adrenaline secretion elicited by insulin-induced hypoglycaemia.

Adrenal Glands↗
PubMed1986

Studies on effects of the substance P analogues [D-Pro2, D-Trp7,9]-substance P and [D-Arg1, D-Trp7,9, L-Leu11]-substance P not related to their antagonist action.

Two tachykinin antagonists, [D-Pro2, D-Trp7,9]-substance P (AP-2) and [D-Arg1, D-Trp7,9, L-Leu11]-substance P (spantide) were injected or infused intraarterially into the isolated perfused rabbit ear connected to the body via the nerve only. The effects of these antagonists on venous outflow, release of histamine, and on acetylcholine-induced reflex fall in blood pressure were recorded. The effect of spantide was also investigated on cholinergic "twitch" responses to the isolated field stimulated ileum of the guinea-pig. Bolus injections of AP-2 (6.6 nmol and 20 nmol) and spantide 20 nmol and 66 nmol i.a. caused a dose-dependent reduction in venous outflow, which could mainly be explained by the release of histamine since the histamine H1 receptor blocker mepyramine inhibited this effect; release of histamine was also directly demonstrated. Injections of AP-2 (20 nmol) and spantide (66 nmol) caused nociceptor stimulation which might in part result from the histamine release. The reflex fall in blood pressure due to nociceptor stimulation by acetylcholine was reduced by less than 30% by infusion of the tachykinin antagonists in a concentration of 12 mumol l-1 but not at 2.4 mumol l-1. Spantide (up to 100 mumol l-1) did not inhibit electrically evoked "twitch" responses of the guinea-pig ileum. The local anaesthetic drug procaine (4.2-42 mumol l-1) inhibited these contractions in a concentration-dependent manner. It is concluded that the tachykinin antagonists might show effects which are not related to their specific tachykinin antagonistic action as indicated by the findings in the rabbit ear.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗
PubMed1986

Distribution of choline acetyltransferase activity in rat spinal cord--influence of primary afferents?

Choline acetyltransferase (CAT) activity was measured in various regions of rat spinal cord. In the ventral cord, enzyme activity was 2 to 3 times higher than in dorsal cord. In dorsal spinal cord, there was a gradient in enzyme activity, increasing CAT activity being observed in more caudal segments. In autonomic regions intermediate levels were measured. Bilateral transection of the sciatic nerve reduced CAT activity in the ventral horn of lumbar spinal cord, whereas CAT activity in the dorsal horn remained unchanged. Capsaicin pretreatment had no effect on CAT activity in any spinal cord region. Although a similar distribution of cholinergic neurones and primary afferent endings in rat dorsal spinal cord was described, no conclusive statement as to a possible functional interaction can be given.

Afferent Pathways↗
PubMed1986

The influence of capsaicin sensitive neurons on stress-induced release of ACTH.

Changes in the plasma levels of ACTH in response to cold exposure or restraint stress were measured in adult rats which had been pretreated with capsaicin or vehicle as neonates. There was no difference in basal ACTH levels between capsaicin and vehicle pretreated animals. Following restraint stress, ACTH levels rose similarly in vehicle and capsaicin pretreated rats, indicating that the pituitary-adrenal system is not impaired by capsaicin pretreatment. However, following cold exposure ACTH levels rose only in control animals whereas no change was observed in capsaicin pretreated animals. It is concluded that capsaicin-sensitive afferent neurons participate in the cold stress-induced increase of plasma ACTH levels.

Adrenocorticotropic Hormone↗
PubMed1985

Opioid control of the function of primary afferent substance P fibres.

Lofentanil, a very potent and long-acting opiate agonist, was used to evaluate the opioid control of substance P release from primary afferents. Substance P release from the central terminals of primary afferents was studied in the superfused isolated dorsal half of the rat spinal cord. Substance P release as initiated by electrical field stimulation and by capsaicin was found to be diminished by 50% by lofentanil (1 microM) in a naloxone-reversible manner. Substance P release from peripheral terminals of primary afferents was induced by antidromic saphenous nerve stimulation. Release was measured indirectly by its effect on blood flow and plasma extravasation in the rat hind paw. Both antidromic vasodilatation and plasma extravasation were dose dependently inhibited by lofentanil. The inhibition of antidromic vasodilatation by 10 micrograms X kg-1 lofentanil i.p. was completely prevented by 1 mg X kg-1 naloxone. On the other hand, vasodilatation and plasma extravasation induced by infusion of 3.7 pmol X min-1 substance P remained unaffected by lofentanil. It is concluded that lofentanil inhibits the release of substance P from central as well as peripheral terminals of substance P-containing primary afferent neurons.

Afferent Pathways↗
PubMed1985

In vivo and in vitro actions of mammalian tachykinins.

Recently, two kassinin-like tachykinins have been isolated from mammalian nervous tissue. The potencies of these peptides, substance K (neurokinin alpha) and neuromedin K (neurokinin beta) were compared with those of substance P, eledoisin, and kassinin in various pharmacological systems in vivo and in vitro. In contracting the isolated guinea-pig ileum and rabbit jejunum the potencies of eledoisin, kassinin, substance K, and neuromedin K were 13-80% that of substance P. In the rat vas deferens substance K and neuromedin K potentiated the electrically induced contractions with potencies similar to those of eledoisin and kassinin; they were 46-236 times as potent as substance P. In stimulating salivation in the rat after intravenous injection, eledoisin, kassinin, and substance K were respectively 2.3, 1.3 and 0.33 times as potent as substance P. In contrast, neuromedin K exhibited negligible activity. Each peptide tested led to a short fall in blood pressure after intravenous injection in the rabbit, substance P being 12-250 times as potent as the other peptides. Substance P was 20 times as potent as substance K or neuromedin K in inducing vasodilatation in the rat hind paw in vivo. Of the peptides tested, only substance P (10 nmol/min) significantly increased the release of histamine from the rat isolated hindquarter preparation. The results are discussed with respect to several theories of tachykinin receptor heterogeneity.

Animals↗
PubMed1985

Release of cholecystokinin-immunoreactivity into the vascular bed of the guinea-pig small intestine during peristalsis.

The release of cholecystokinin-immunoreactivity (CCK-IR) into the venous effluate of the isolated and vascularly perfused guinea-pig small intestine was measured. Raising the intraluminal pressure by 5 mbar for 8 min initiated peristalsis and was associated with an increased release of CCK-IR. The ganglion stimulant dimethylphenyl-piperazinium failed to alter the release of CCK-IR. The results are discussed in the light of a possible involvement of CCK-containing neurones in intestinal peristalsis.

Animals↗
PubMed1985

Characterization of substance P-like immunoreactivity in submammalian species by high performance liquid chromatography.

Substance P-like immunoreactivity (SP-LI) as measured by RIA was found to be present in a variety of submammalian species and invertebrates. We analyzed this SP-LI in extracts from submammalian species by high performance liquid chromatography. The following species were investigated for the presence of SP-LI (RIA) which was further characterized by subsequent HPLC (investigated areas in parentheses): Hagfish (brain plus spinal cord), (brain, intestine, skin), frog (brain, intestine), turtle (brain, intestine), lizard (brain, intestine, skin) and mouse (spinal cord). RIA alone was performed in extracts from branchiostoma and cricket. The concentrations of SP-LI in brain, spinal cord and intestine of different submammalian species except branchiostoma brain and intestine and turtle brain, were in a similar range (2.1-5.3 fmol/mg in the brain, 0.2-2.0 fmol/mg in the spinal cord, 0.3-4.2 fmol/mg in the intestine). In the turtle brain, extremely high SP-LI concentrations (210 fmol/mg) were found, whereas brain and intestine of branchiostoma contained very little SP-LI (0.1 fmol/mg). In the skin of different species, SP-LI concentrations varied from 0.04 fmol/mg (trout) to 2.0 fmol/mg (lizard). In the cricket, high SP-LI concentrations were found in the cerebral ganglion (15 fmol/mg protein) and in the subesophageal ganglion (27 fmol/mg protein). HPLC analysis of extracts showed that all tissues investigated contained a substance which co-eluted with synthetic SP, and in most tissues a peak was present which co-eluted with SP sulfoxide. Only in mouse spinal cord, trout brain and hagfish brain were these the only peaks.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1985

New models for the evaluation of opioid effects in the guinea-pig ileum.

The pharmacology of morphine and opioid peptides was studied in the guinea-pig ileum by examining their inhibitory effects on propulsive peristaltic activity and on the cooling-induced longitudinal contraction. In these experiments, dose-response curves were recorded. The rank order of potency in inhibiting peristalsis was found to be: dermorphin greater than FK 33-824 greater than dynorphin-(1-17) greater than dynorphin-(1-13) greater than delta-receptor-peptide greater than morphine greater than [Leu] enkephalin, whereas the rank order in inhibiting cooling-induced contractions was found to be: dynorphin-(1-13) congruent to FK 33-824 congruent to dermorphin greater than delta-receptor peptide greater than morphine. Naloxone antagonized the maximally effective dose of each of the opioid agents. In view of the differences between the abilities of these opioids to inhibit propulsive peristaltic activity, these models seem to be valuable for the examination of inhibitory opioid effects in the gut.

Animals↗
PubMed1984

Immunoreactive substance P in the tubero-hypophyseal system of the rat: selective decrease in the neural lobe after dehydration and sodium loading.

In the tubero-hypophyseal system of the rat the approximate concentrations of immunoreactive substance P (I-SP), expressed as fmol/mg tissue, were 100 in the medial basal hypothalamus (MBH), 20 in the anterior lobe (AL), 20 in the neural lobe (NL) and 4 in the intermediate lobe of the hypophysis. These values were not altered by treatment with capsaicin on day 2 after birth. In rats in which the secretion of neurohormones from the NL was increased by dehydration followed by sodium loading there was a fall by 70% in the I-SP concentration of the NL; no change occurred in the AL or the MBH.

Animals↗
PubMed1984

Substance P immunoreactivity in the rat mammary nipple and the effects of capsaicin treatment on lactation.

Tissue concentrations of substance P immunoreactivity (SP-I) were measured in rat mammary nipples and were significantly greater than in ventral abdominal skin in nonpregnant and pregnant rats. In contrast, the concentration of nipple SP-I was lower than that of skin in twelve day lactating animals. The mean total SP-I content of the pooled twelve nipples from each rat was not significantly different in nonpregnant, pregnant or lactating rats. However, the mean weight of the pooled twelve nipples from each rat was significantly higher in the lactating rats than in pregnant rats. Immunohistochemistry revealed SP-I nerve trunks and single fibers throughout the nipples of lactating rats. Nerve fibers were observed among smooth muscle and along blood vessels throughout the dermis and in association with epidermal structures. Some SP-I fibers were also observed in association with the main lactiferous duct and mammary gland secretory parenchyma. Radioimmunoassay and immunohistochemistry of nipples from lactating rats treated with capsaicin as neonates revealed a marked depletion of SP-I. Rats treated with capsaicin as neonates had a normal gestation period and produced litters of normal size and birth weight. However, the litters of these lactating rats grew at a significantly slower rate than litters from controls. The quantity of milk obtained from capsaicin-treated lactating dams, following a one hour suckling period on the twelfth day of lactation, was significantly less than that obtained by litters of control dams. It is concluded that capsaicin-sensitive primary sensory nerves of the mammary nipple play a role in the afferent limb of the suckling reflex. One transmitter candidate for these nerves is substance P.

Animals↗
PubMed1984

Effect of neonatal treatment with capsaicin on carrageenan-induced paw oedema in the rat.

The time course of the paw oedema induced by the subplantar injection of carrageenan was studied in rats treated neonatally with capsaicin and in their vehicle-treated controls. In the capsaicin-treated rats, which show a permanent deficit of unmyelinated primary sensory neurones, carrageenan produced an oedema which was larger and lasted longer than in the vehicle-treated rats. Pretreatment with the histamine liberator compound 48/80 reduced the carrageenan-induced paw oedema only in the capsaicin-treated rats whereas pretreatment with indomethacin reduced it in both groups of rats. The increased and prolonged inflammatory response to carrageenan in capsaicin-treated rats may be explained by an enhanced release of histamine from mast cells and may also reflect a 'trophic disorder of the denervated skin'.

Animals↗
PubMed1984

Substance P in primary afferent neurons of the female rat reproductive system.

The amount of substance P-immunoreactivity (SP-I) was studied in the female rat reproductive organs (uterus, cervix, vagina and ovary) in the diestrous and estrous stages of the estrous cycle, after ovariectomy and on days 7, 14 and 19 of pregnancy. The concentration of SP-I (pmol X g-1 tissue) was generally highest in the vagina followed by cervix, uterus and ovary. SP-I concentrations in all reproductive organs were significantly higher following ovariectomy but significantly lower during pregnancy compared to concentrations from intact rats. There were no significant differences in the total content of SP-I per organ during the estrous cycle, after ovariectomy or during pregnancy (cervix, vagina). SP-I concentrations were markedly reduced in the reproductive organs of adult rats treated with capsaicin as neonates. This led to the conclusion that SP in reproductive organs is present in primary afferent fibers. The findings indicate that the number of SP-I containing primary afferent fibers in the female reproductive organs are stable elements neither increasing nor decreasing in response to changing hormonal levels or to the tissue growth and differentiation occurring during the estrous cycle or pregnancy.

Animals↗
PubMed1984

The effects of neonatal capsaicin treatment on growth and subsequent reproductive function in the rat.

The results of the present study describe the following effects of neonatal capsaicin treatment on growth and reproductive function in the rat. Neonatal capsaicin treatment in the rat resulted in a retardation of body growth through adulthood most pronounced at 35 days of age. Capsaicin-treated rats had normal estrous cycles, but mated significantly less frequently than age-matched controls. Confirmed matings in capsaicin-treated female rats resulted in significantly fewer pregnancies compared to controls. Male rats treated with capsaicin as neonates produced significantly fewer pregnancies when mated with untreated females compared to controls. Ovulation, sperm transport, and fertilization occur normally in capsaicin-treated rats. The decidual response was markedly diminished in mated capsaicin-treated rats. These findings led to the conclusion that the neurohormonal reflex, which is normally initiated through the stimulation of the cervix by copulation, and which ultimately stimulates secretion of pituitary luteotropic hormones, did not occur in capsaicin-treated rats. Thus, ovarian progesterone secretion was not facilitated resulting in inadequate hormonal support for implantation, pregnancy or pseudo-pregnancy. These data further suggest that the sensory limb of this neurohormonal reflex may consist of capsaicin-sensitive, possibly substance P containing, primary afferent fibers.

Animals↗