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C Wahlestedt

Publications and source records attributed to C Wahlestedt.

At least 91 records · Page 5Linked to original sources
PubMed1989

Effects of psychoactive drugs on delta sleep-inducing peptide concentrations in rat brain.

The concentration of delta sleep-inducing peptide-like immunoreactivity (DSIP-LI) in rat brain regions was determined by radioimmunoassay following treatment with various psychoactive drugs or adrenalectomy. The antidepressant drugs imipramine and zimeldine, given orally twice daily for three weeks, reduced the concentrations of DSIP-LI in the hypothalamus, frontal cortex and cerebellum. The effects of zimeldine were similar but somewhat less pronounced than those of imipramine. The neuroleptic drug haloperidol, given i.p. once daily for two weeks, increased the concentration of DSIP-LI in the hypothalamus, but not in the frontal cortex. A single dose of haloperidol did not affect the concentration of DSIP-LI in either region. Like haloperidol, pentobarbital elevated the concentration of DSIP-LI in the hypothalamus; however, this effect of the barbiturate was seen after single but not after repeated administration. Cortical concentrations of DSIP-LI were unaffected following both single and repeated pentobarbital administration. Finally, adrenalectomy increased the concentration of DSIP-LI in the hypothalamus, but not in the other brain regions. In conclusion, the DSIP concentration in rat brain regions may be altered by a variety of interventions. The most profound and general alterations were observed following administration of antidepressant drugs.

Adrenalectomy↗
PubMed1989

Neuropeptide Y (NPY) and the central nervous system: distribution effects and possible relationship to neurological and psychiatric disorders.

1. NPY is a 36 amino acid tyrosine-rich peptide. It is one of the most abundant and widely distributed neuropeptides known today within the central nervous system with particularly high concentrations in the hypothalamus and in several limbic regions. 2. NPY seems to coexist with other on neurotransmitters like somatostatin, galanin, GABA and the catecholamines noradrenaline and adrenaline in discrete brain regions. 3. NPY binding sites are widely distributed in the brain. However they do not always overlap with the distribution of NPY-like immunoreactivity. 4. NPY is suggested to be involved in a large number of neuroendocrine functions, stress responses, circadian rhythms, central autonomic functions, eating and drinking behaviour, and sexual and motor behaviour. 5. Psychotropic drugs and neurotoxins can alter the NPY concentrations in discrete brain regions. 6. It is possible that NPY is related to various neurological and psychiatric illnesses, like Huntington's chorea, Alzheimer's disease, Parkinson's disease, eating disorders, and major depressive illness.

Animals↗
PubMed1988

Neuropeptide Y (NPY)-induced suppression of activity in the rat: evidence for NPY receptor heterogeneity and for interaction with alpha-adrenoceptors.

The receptor mechanisms mediating the neuropeptide Y (NPY)-induced suppression of behavioural activity have been examined in the rat. The interaction of NPY with central noradrenergic mechanisms was also studied. The non-selective alpha-adrenoceptor antagonist, phentolamine (15-60 nmol intracerebroventricularly, i.c.v.), caused a dose-related antagonism (up to 50%) of the NPY-induced suppression of activity. The selective alpha 2-adrenoceptor antagonist, idazoxan (0.125 mg/kg intraperitoneally, i.p.), was even more effective, while the selective alpha 1-adrenoceptor antagonist, prazosin, was without effect. In addition, we examined whether the recently postulated subdivision of peripheral NPY receptors was also applicable to the brain. The ability of the C-terminal 13-36 amino acid fragment of NPY (postulated to activate NPY-Y2 receptors) to reproduce the effects of the full molecule (postulated to activate both NPY-Y1 and -Y2 receptors) was tested. NPY-(13-36) (0.4-10.0 nmol i.c.v.) failed to produce any suppression of activity. On the contrary, it produced an increase in locomotor activity and rearings at low doses. This effect was not blocked by phentolamine. We conclude that the NPY-induced suppression of activity is produced to a large extent by modulation of alpha 2-adrenergic transmission. Our results also provide evidence for heterogeneity among the central NPY receptors, with the NPY-induced suppression of activity being mediated by the NPY-Y1 receptor subtype.

Animals↗
PubMed1988

Antidepressant drugs increase the concentration of neuropeptide Y (NPY)-like immunoreactivity in the rat brain.

Rats were given imipramine or zimeldine orally for three weeks and the brain levels of neuropeptide Y-like immunoreactivity (NPY-LI) were measured. The concentration of NPY-LI in frontal cortical tissue was elevated by 40 and 60%, respectively. Imipramine increased the concentration of NPY-LI in the hypothalamus by 65% while zimeldine was without effect. The concentration of NPY-LI in the parietal cortex was unaffected by either of the drugs. These observations support the hypothesis that NPY might be involved in the pathophysiology of depressive illness.

Animals↗
PubMed1988

Neuropeptide Y and peptide YY as possible cerebrospinal fluid markers for major depression and schizophrenia, respectively.

Neuropeptide Y (NPY)-like and peptide YY (PYY)-like immunoreactivities were measured in cerebrospinal fluid (CSF) from patients with major depressive disorder or schizophrenia and from healthy volunteers without physical or mental illness. NPY-like material was significantly lower (P less than 0.001) in CSF of patients with depressive disorders than in schizophrenic patients or healthy controls. Treatment with the antidepressant, amiflamine, a selective MAO-A inhibitor, did not alter CSF peptide concentrations. In drug-free schizophrenic patients, normal NPY but reduced PYY concentrations in CSF were observed. Treatment with neuroleptics did not affect the levels of NPY or PYY in the CSF. The finding of reduced CSF concentrations of NPY in patients with major depression and of reduced PYY concentrations in schizophrenia may reflect disturbed synthesis, turnover or degradation of the peptides. These findings suggest that the reduced concentrations of NPY or PYY in the CSF may be used as trait markers of the respective illnesses.

Adolescent↗
PubMed1988

The effect of neuropeptide Y and peptide YY on electrogenic ion transport in rat intestinal epithelia.

1. Neuropeptide Y (NPY), peptide YY (PYY) and, to a lesser extent, human pancreatic polypeptide (HPP) reduced short-circuit current (SCC) in a concentration-dependent manner in epithelial preparations of rat jejunum and descending colon. 2. From concentration-response curves in the jejunum EC50 values of 3 nM for PYY and 10 nM for NPY were obtained. HPP was much less potent, the threshold concentration being around 100 nM, and NPY 13-36 was inactive. 3. Repeated exposure of jejunal preparations to either NPY or PYY led to a rapid desensitization. Cross-desensitization to the actions of these two peptides was also observed. Neither tetrodotoxin (TTX) nor phentolamine affected responses to either NPY or PYY on the jejunum. 4. Responses to both peptides were inhibited by the presence of transport inhibitors, particularly diphenylamine-2-carboxylate (DPC, a chloride channel blocker) and piretanide (Na+-K+-2Cl- co-transport inhibitor). These results may indicate that the reduction in SCC caused by the neuropeptides is due to a net increase in chloride movement in the apical to basolateral direction. 5. 36Cl-flux studies identified an inhibition of chloride secretion as the predominant mechanism of action of NPY and PYY, together with a smaller stimulation of chloride absorption. No significant changes in the movement of 22Na were seen in either direction. 6. The cyclo-oxygenase inhibitors piroxicam (5 microM) and indomethacin (5 microM) significantly reduced the responses to both NPY and PYY in rat jejunum. From this and other evidence it was concluded that the peptides depended for their effect on the endogenous formation of eicosanoids, the prevention of which attenuated the SCC reduction due to the peptides.

Animals↗
PubMed1987

Neuropeptide Y (NPY) in the area of the hypothalamic paraventricular nucleus activates the pituitary-adrenocortical axis in the rat.

Immunocytochemical studies have documented the presence of neuropeptide Y (NPY) in the hypothalamic paraventricular nucleus (PVN) which harbours a large number of neurones that contain corticotrophin-releasing factor (CRF). In this study the close morphological association between NPY fibres and CRF cell bodies in the PVN was confirmed. The localization of NPY terminals in the vicinity of CRF neurones forms a morphological basis for an action of NPY in the hypothalamic control of the pituitary-adrenocortical axis. We therefore microinjected NPY into the area of the PVN of both conscious, freely moving and anaesthetized rats and noted a powerful stimulatory effect on adrenocorticotropic hormone (ACTH) and corticosterone release as measured by radioimmunoassay. In experiments with conscious, freely moving rats, higher ACTH and corticosterone levels were detected following injection of NPY into the area of the PVN than following control injection (desamidated NPY). Intracerebroventricular injection of NPY produced a small, albeit significant, increase in circulating corticosterone levels as compared to control (saline-injected) rats. Anaesthetized rats responded to NPY (but not to saline) injected into the area of the PVN with elevated ACTH and corticosterone levels, while injection of NPY into the neocortex failed to affect the blood concentration of either ACTH or corticosterone. In conclusion, we have demonstrated an activating effect of NPY on the pituitary-adrenocortical axis both in conscious and anaesthetized rats which may reflect the anatomical relationship between NPY fibres and CRF neurones in the PVN.

Adrenocorticotropic Hormone↗
PubMed1987

Multiple tachykinin pools in sensory nerve fibres in the rabbit iris.

A population of sensory nerve fibres in the rabbit iris is known to contain calcitonin gene-related peptide and tachykinins, such as substance P and neurokinin A. In the presence of atropine and guanethidine, the isolated iris sphincter responded to electrical stimulation with a contraction that could be abolished by tachykinin antagonists. Capsaicin, known to release tachykinins from sensory fibres, evoked a long-lasting tachykinin-mediated contraction of the iris sphincter. Repeated application of capsaicin led to tachyphylaxis, possibly reflecting depletion of releasable neuronal stores of tachykinins. At this stage, electrical stimulation failed to elicit contraction. The capacity of capsaicin to release neuropeptides from sensory fibres was confirmed by determination of substance P- and calcitonin gene-related peptide-like immunoreactivity in the incubation medium and in the iris tissue. The concentrations of substance P and calcitonin gene-related peptide in the iris after capsaicin exposure were reduced by about 25%. Like capsaicin, bradykinin evoked a tachykinin-mediated contraction and tachyphylaxis. However, after development of tachyphylaxis to bradykinin, electrical stimulation or exposure to capsaicin still evoked tachykinin-mediated contraction, albeit a reduced one compared with the response before bradykinin. Hence, capsaicin completely depletes tachykinin stores releasable by prolonged electrical stimulation, whereas bradykinin exhausts only a sequestered pool. The possibility that tachykinins occur in several releasable pools in sensory nerves was investigated in yet another way: the iris sphincter muscle was stimulated electrically once every 2.5 min over several hours. The contractile response diminished gradually.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Hirschsprung's disease: a comparison of the nervous control of ganglionic and aganglionic smooth muscle in vitro.

Specimens from aganglionic (constricted) and ganglionic (dilated) gut were obtained from nine patients with Hirschsprung's disease. Transmural nerve stimulation of ganglionic smooth muscle in vitro evoked an initial relaxation followed by a contraction. This contraction was reduced but not abolished by atropine and it was further reduced by substance P antagonists. Guanethidine did not affect the electrically evoked responses. In aganglionic smooth muscle, an atropine-sensitive contraction but no initial relaxation was registered. Tetrodotoxin abolished all responses to electrical stimulation in both ganglionic and aganglionic specimens. Application of carbachol or substance P produced contraction and the adrenergic agonist isoprenaline or vasoactive intestinal peptide produced relaxation in ganglionic as well as aganglionic specimens. Two other gut neuropeptides, neuropeptide Y and galanin, were without effect. The results do not indicate a different receptor set up in ganglionic v aganglionic gut. The results are compatible with a lack of noncholinergic nonadrenergic inhibitory neurons in the aganglionic gut.

Child↗
PubMed1987

Effects of neuropeptide Y (NPY) on isolated guinea-pig heart.

Neuropeptide Y (NPY) is present in nerve fibres throughout the mammalian heart. We have elucidated the effects of NPY on the isolated papillary muscle and heart (Langendorff) from the guinea-pig. The paced papillary muscle was studied with regard to duration of the action potential, peak force, maximum rate of force development, time to peak force, and time from peak force to half relaxation; all these parameters were identical whether or not NPY (5 X 10(-7) M) was present in the medium. When a stimulation with trains of pulses was superimposed, the paced papillary muscle exhibited enhanced contractions. This increase in contractility was not observed in the presence of the beta-adrenoceptor antagonist propranolol (10(-6) M) and was thus considered to be adrenergically mediated. The latter (adrenergic) response was markedly attenuated by NPY. Since NPY did not interfere with the response to exogenous noradrenaline (NA) it is suggested that the peptide exerts a pre-junctional inhibitory affect on adrenergic nerve-mediated positive inotropy. Neuropeptide Y did not influence the electrocardiogram from the spontaneously beating heart (Lagendorff), nor did the peptide modify the positive chronotropic effect of exogenously applied NA. In conclusion, the results indicate that NPY is without effect on the heart muscle proper but that the sympathetic terminals of the heart possess pre-junctional receptors for NPY (and/or related peptides) related to suppression of stimulated NA release.

Action Potentials↗
PubMed1987

GABA suppresses stimulation-induced release of [3H]-noradrenaline from sympathetic nerve fibres in bovine ovarian follicles.

1 Strips from the bovine ovarian follicle wall were incubated in Krebs-Ringer solution containing [3H]-noradrenaline in order to saturate sympathetic nerve fibres with radiolabelled transmitter. This allowed the study of field stimulation-evoked transmitter release. 80.3 +/- 3.9% of the tritium released upon stimulation (10 Hz, pulse duration 1 ms, 10 V between the electrodes) was noradrenaline. 2 The stimulated release of tritium was totally blocked in calcium-free, EGTA (1 mM) containing medium or by 1 microM tetrodotoxin. Chemical sympathectomy (6-hydroxydopamine treatment) in vitro reduced the tritium content of the strip by 85%. The neuronal amine uptake blocker desipramine (0.6 microM) was almost equally effective in inhibiting the incorporation of tritium. The extraneuronal amine uptake blocker normetanephrine (10 microM) reduced the tritium content by 30%. Together, the results suggest that the electrically evoked release of tritium reflects the release of [3H]-noradrenaline from sympathetic nerve fibres. 3 gamma-Aminobutyric acid (GABA) concentration-dependently reduced the electrically evoked tritium release. Also the GABAB-receptor agonist baclofen (30 microM) reduced the stimulated tritium release whereas muscimol (100 microM), a GABAA-receptor agonist, failed to affect the release. 4 The selective GABAA-receptor antagonist bicuculline (3 and 100 microM) did not block the effect of GABA, while 3-amino-1-propanesulphonic acid (3-APA), a blocker of GABAB-receptors reversed the inhibitory effect of GABA. The results suggest that neuronal GABAB-receptors are involved in the GABA-evoked suppression of stimulated noradrenaline release.

Animals↗
PubMed1986

Calcitonin gene-related peptide in the eye: release by sensory nerve stimulation and effects associated with neurogenic inflammation.

Calcitonin gene-related peptide (CGRP) in the anterior uvea coexists with tachykinins (substance P and neurokinin A) in sensory nerve fibers deriving from the trigeminal ganglion. Mechanical or electrical stimulation of the intracranial part of the trigeminal nerve/ganglion in rabbits produced a marked hyperemia in the anterior segment of the eye, increased intraocular pressure, breakdown of the blood-aqueous barrier and miosis. Simultaneously, CGRP-like immunoreactivity was released into the aqueous humor. This suggests that the highly vasoactive CGRP can be released from sensory nerve fibers to participate in vascular responses. Unlike the tachykinins, CGRP per se was without effect on the pupillary diameter while disrupting the blood-aqueous barrier (resulting in aqueous flare) upon intravitreal injection. In addition, CGRP enhanced the aqueous flare evoked by a minimal eye trauma (infrared irradiation of the iris). The miosis evoked by the intravitreal injection of substance P was more pronounced when CGRP was injected simultaneously, and finally, substance P induced aqueous flare much more effectively when given together with a threshold dose of CGRP.

Animals↗
PubMed1986

Peptide YY-like immunoreactivity in the central nervous system of the rat.

The concentration of peptide YY (PYY)-like immunoreactivity in rat brain and spinal cord was determined by radioimmunoassay. The highest concentrations were found in the cervical spinal cord (18.1 +/- 1.3 ng/g, mean +/- S.E.M.) and in the medulla oblongata (16.3 +/- 1.5 ng/g). Lower amounts were found in the pons and in the hypothalamus. Chromatographic analysis of the PYY-like immunoreactivity from various regions of the brain revealed 95% of the immunoreactive material to be indistinguishable from synthetic porcine PYY. PYY-immunoreactive nerve cell bodies could be demonstrated by immunocytochemistry in the medulla oblongata of colchicine-treated rats, the largest group of cells being found in the midline area between and partly in the raphe pontis and obscurus nuclei. Another large group of immunoreactive cells was detected more laterally in the medial parts of the gigantocellular reticular nucleus. A few cells, finally, were seen in the dorsal parts of the medulla, including the nucleus of the solitary tract. Varicose nerve fibers displaying PYY immunoreactivity were observed in many parts of the hypothalamus, pons, medulla and spinal cord.

Animals↗
PubMed1986

Evidence for different pre-and post-junctional receptors for neuropeptide Y and related peptides.

The effects of neuropeptide Y (NPY), peptide YY (PYY), desamido-NPY and five C-terminal fragments of NPY or PYY were tested on different smooth muscle preparations in vitro. The fragments were NPY 19-36, NPY 24-36, PYY 13-36, PYY 24-36 and PYY 27-36. NPY and PYY appear to exert three principally different effects at the level of the sympathetic neuroeffector junction. Firstly, they have a direct post-junctional effect, leading to constriction of certain blood vessels; this was studied on the guinea-pig iliac vein. Secondly, they potentiate the response to various vasoconstrictors; this was studied on the rabbit femoral artery and vein, using noradrenaline and histamine, respectively, as agonists. Thirdly, NPY and PYY act prejunctionally in that they suppress the release of noradrenaline from sympathetic nerve endings upon stimulation; this was studied in the rat vas deferens. NPY and PYY were approximately equipotent in constricting the guinea-pig iliac vein, while desamido-NPY and the fragments were without effect. Desamido-NPY and the fragments were ineffective also in potentiating the response to noradrenaline in the rabbit femoral artery, nor did they potentiate the response to histamine in the rabbit femoral vein. NPY and PYY potentiated the response to noradrenaline in the artery, as well as the response to histamine in the vein. The NPY- and PYY-induced suppression of noradrenaline release from the prostatic portion of the rat vas deferens was reproduced by PYY 13-36 but not by the shorter fragments nor by desamido-NPY. In conclusion, a C-terminal portion seems to be sufficient for exerting the prejunctional effect of NPY and PYY, while the whole sequence seems to be required for post-junctional (direct and modulatory) effects. An amidated C-terminal is crucial for maintaining the biological activity of NPY. Desamido-NPY and the fragments that were inactive as agonists also seemed inactive as antagonists.

Animals↗
PubMed1986

Effects of neuropeptide Y (NPY) at the sympathetic neuroeffector junction. Can pre- and postjunctional receptors be distinguished?

Neuropeptide Y (NPY) is widely distributed in central and peripheral neurons. In sympathetic postganglionic neurons, NPY coexists with noradrenaline. NPY and its structural relative peptide YY (PYY) appear to exert three principally different effects at the sympathetic neuroeffector junction. Firstly, NPY has a direct postjunctional effect; this effect is manifested as a vasoconstriction when studied on the guinea pig iliac vein. Secondly, NPY has an indirect postjunctional effect in that it potentiates the response to various vasoconstrictors; this was studied on the rabbit femoral artery and vein, using noradrenaline and histamine, respectively, as vasoconstrictors. Thirdly, NPY acts prejunctionally in that it suppresses the release of noradrenaline from sympathetic nerve terminals; this was studied in the rat vas deferens. The aim of the investigation was to examine whether the three effects of NPY were mediated by the same type of receptor. For this purpose, we examined the effects of a series of NPY-related peptides, namely NPY, PYY, desamido-NPY, and five C-terminal fragments (NPY 19-36, NPY 24-36, PYY 13-36, PYY 24-36 and PYY 27-36). NPY and PYY were active in all three assay systems. The C-terminal amide appears to be crucial for maintaining the biological activity, since desamido-NPY was inactive in the three test systems. Interestingly, PYY 13-36 was almost as active as NPY and PYY in suppressing the electrically evoked contractions of the vas deferens; PYY 13-36 was inactive in the two other test systems. None of the shorter fragments had any biological activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic Fibers↗
PubMed1985

Neurogenic mechanisms in control of the rabbit iris sphincter muscle.

The iris sphincter muscle is supplied with cholinergic, adrenergic and substance P-containing nerve fibers, all with a possible role in the control of pupil size. The functional significance of the various nervous components in the rabbit iris sphincter muscle was examined in vitro and in vivo. The contractile response to electrical stimulation is composed of several contractions, occurring along different time scales. Single pulse stimulation produced an atropine-sensitive twitch. Pulse train stimulation revealed two successive atropine-sensitive twitches followed by a slow, long-lasting contraction, sensitive to Spantide, an antagonist of tachykinins such as substance P. A guanethidine- and phentolamine-sensitive contractile response to pulse train stimulation could be demonstrated in the presence of both atropine and Spantide. Only the Spantide-sensitive response could be completely exhausted by prolonged electrical stimulation. In vivo, neither the adrenergic nor the substance P-containing nerve fibres appeared to contribute to the miotic response to light since Spantide and guanethidine were without effect. This response was inhibited by atropine only.

Animals↗