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Biomedical subjects

C Wahlestedt

Publications and source records attributed to C Wahlestedt.

103 records · Page 6Linked to original sources
PubMed1985

Pupillary supersensitivity to substance P following prolonged treatment with tetrodotoxin or substance P antagonists.

Pilocarpine contracts the sphincter pupillae muscle via an effect on muscarinic receptors and phenylephrine contracts the dilator pupillae muscle via an effect on alpha-adrenergic receptors. These effects are thought to mimic the action of the parasympathetic and sympathetic nervous systems, respectively. Intracellular injection of substance P (SP) produces an atropine-resistant constriction of the pupil. This response is thought to mimic the effect of local sensory reflexes on the sphincter pupillae muscle, involving SP-containing trigeminal nerve endings. Repeated intraocular injections of tetrodotoxin, a general blocker of nervous conduction, over a period of 3 weeks produced supersensitivity to pilocarpine, phenylephrine and SP in the rabbit iris. These findings support the view that, like acetylcholine and noradrenaline, SP or an SP-like compound acts as a neurotransmitter in the iris. Also, long-term topical application of an SP antagonist, (D-Pro2,D-Trp7,9)-SP or (Arg5,D-Trp7,9)-SP5-11, to the rabbit eye produced supersensitivity to SP but not to pilocarpine, thus supporting the view that the SP antagonists interact specifically with the SP receptors. The isolated rabbit iris sphincter muscle responds to electrical stimulation with a cholinergic twitch followed by a slow non-cholinergic contraction that can be blocked by antagonists to SP. Analysis of the motor activity of the iris sphincter muscle after long-term topical treatment of the eye with an SP antagonist followed by an interval of 2 days after termination of treatment revealed a greatly enhanced non-cholinergic contraction compared with the cholinergic twitch, a finding that seems to be consistent with the idea that supersensitivity to SP had developed.

Animals↗
PubMed1985

Spinal projections of hypothalamic histidine decarboxylase-immunoreactive neurones.

The existence of a histidine decarboxylase (HDC)-immunoreactive diencephalo-spinal pathway in the rat was demonstrated using an antiserum raised against HDC from fetal rat liver. HDC-immunoreactive nerve cell bodies were numerous in the ventral and lateral caudal hypothalamus. More caudally, in the mesencephalon, no cell bodies were observed but fairly many, transversely cut nerve fibres were found in association with the fasiculus longitudinalis medialis bilaterally. At the most caudal medullary level these longitudinally passing fibres became displaced ventrally to a position just laterally to the pyramidal decussation. In the spinal cord the fibres were more dispersed and rather sparse in most areas. The existence of a diencephalo-spinal HDC-immunoreactive pathway was verified by analyzing material from rats which had received injections of the retrograde fluorescent tracer True Blue into the cervical spinal cord. True Blue fluorescence and HDC immunofluorescence were found to coexist in a subpopulation of the HDC-immunoreactive neurones in the hypothalamus.

Animals↗
PubMed1985

Innervation of human omental arteries and veins and vasomotor response to noradrenaline, neuropeptide Y, substance P and vasoactive intestinal peptide.

Human omental arteries and veins are supplied with nerve fibers containing noradrenaline (NA) and neuropeptide Y (NPY); these two agents probably co-exist in perivascular sympathetic nerve fibers. Substance P (SP)- or vasoactive intestinal peptide (VIP)-containing fibers could not be detected. In studies on isolated omental vessels NA produced constriction. The results of blockade experiments suggest that human omental arteries are equipped predominantly with alpha 1-adrenoceptors and omental veins with a mixture of alpha 1- and alpha 2-adrenoceptors. NPY at a concentration of 10(-7) M or higher had a weak contractile effect on veins and virtually no effect on arteries. NPY at a concentration of 3 X 10(-8) M shifted the NA concentration response curve to the left in arteries (pD2 = 5.8 for NA versus 6.6. for NA in the presence of NPY; P less than 0.001) but not in veins. Both SP and VIP relaxed arteries precontracted with NA or prostaglandin F2 alpha (PGF2 alpha). The potency of SP as a relaxant agent was similar in arteries and veins; the effect of VIP was elicited at lower concentrations in veins than in arteries.

Aged↗
PubMed1985

Galanin: neuromodulatory and direct contractile effects on smooth muscle preparations.

The effects of galanin, a newly isolated neuropeptide, and of a galanin fragment (galanin 1-10) were studied on various smooth muscle preparations in vitro. Direct motor effects as well as effects on electrically induced (neuronally mediated) responses (neuromodulatory effects) were observed. Both gatanin and galanin 1-10 evoked a strong contractile response in rat jejunal longitudinal muscle. This effect was a direct one on the smooth muscle. Addition of galanin to guinea-pig taenia coli inhibited the contractile response to electrical stimulation, mediated by endogenous substance P and acetylcholine. In the rabbit iris sphincter, galanin reduced the acetylcholine-mediated but not the substance P-mediated contraction evoked by electrical stimulation. The neuromodulatory effects seem to be presynaptic and require the whole or possibly only the C-terminal part of the galanin molecule, since galanin 1-10 was ineffective. Rabbit femoral artery and vein, gastroepiploic and basilar arteries and guinea-pig trachea and main bronchi did not respond to either galanin or galanin 1-10.

Animals↗
PubMed1985

Neuropeptide Y potentiates noradrenaline-evoked vasoconstriction: mode of action.

Neuropeptide Y (NPY), which co-exists with noradrenaline (NA) in postganglionic sympathetic nerves, was able to potentiate NA-evoked constriction in certain isolated rabbit blood vessels. The phenomenon was observed in the femoral, the gastroepiploic and the pulmonary arteries but not in the femoral or the gastroepiploic veins or in the aorta. Thus, NPY potentiated NA-evoked vasoconstriction predominantly in muscular arteries with alpha-1 adrenoceptors. NPY-related peptides, such as peptide YY and to some extent pancreatic polypeptide shared this ability, whereas calcitonin gene-related peptide or LPLRFamide did not. The mode of action by which NPY potentiates NA-evoked vasoconstriction was analyzed using the femoral artery. Pretreatment of the vessel with cocaine, a blocker of amine re-uptake, or rolipram, an inhibitor of phosphodiesterase, left the potentiation unaffected, whereas Na+ deficiency or ouabain, an inhibitor of Na+/K+-adenosine triphosphatase, abolished this effect of NPY. Nifedipine, a blocker of Ca++ entry, or removal of extracellular Ca++ shortly before the application of NPY had little effect. After prolonged exposure to a Ca++-free medium (with ethylene glycol bis(beta-aminoethyl ether)-N,N'-tetraacetic acid) the maximum response to NA was greatly reduced and the potentiating effect of NPY was abolished. Thus, the potentiation of NA-evoked vasoconstriction by NPY seems to depend upon the presence of Na+ but not upon a Ca++ influx. An intracellular sequestered Ca++ pool appears to play a critical role.

Animals↗
PubMed1984

Pupillary constriction by bradykinin and capsaicin: mode of action.

The application of bradykinin or capsaicin to the rabbit eye evoked strong miosis. The effect could be prevented by pretreatment of the eye with tetrodotoxin (TTX) or a substance P (SP) antagonist. However, the miotic response could be elicited despite TTX or the SP antagonist if the dose of capsaicin or bradykinin was increased. Bradykinin and capsaicin contracted the isolated rabbit sphincter pupillae muscle. The contraction produced by bradykinin and capsaicin was unaffected by TTX but reduced by specific SP antagonists. This indicates that bradykinin and capsaicin exert their effects on the isolated sphincter muscle through the release of SP but independent of neuronal conduction. In vivo, the situation seems to be different. The finding that TTX is capable of blocking the miotic response to moderate doses of bradykinin and capsaicin suggests that the effect on the eye under these circumstances is dependent upon a normal impulse traffic.

Animals↗
PubMed1984

Neuropeptide Y co-exists and co-operates with noradrenaline in perivascular nerve fibers.

Neuropeptide Y (NPY)-immunoreactive nerve fibers were numerous around arteries and few around veins. NPY probably co-exists with noradrenaline in such fibers since chemical or surgical sympathectomy eliminated both NPY and noradrenaline from perivascular nerve fibers and since double staining demonstrated dopamine-beta-hydroxylase, the enzyme that catalyzes the conversion of dopamine to noradrenaline, and NPY in the same perivascular nerve fibers. Studies on isolated blood vessels indicated that NPY is not a particularly potent contractile agent in vitro. NPY greatly enhanced the adrenergically mediate contractile response to electrical stimulation and to application of adrenaline, noradrenaline or histamine, as studied in the isolated rabbit gastro-epiploic and femoral arteries. The potentiating effect of NPY on the response to electrical stimulation is probably not presynaptic since NPY affected neither the spontaneous nor the electrically evoked release of [3H]noradrenaline from perivascular sympathetic nerve fibers.

Animals↗
PubMed1984

Neuropeptide Y potentiates the effect of various vasoconstrictor agents on rabbit blood vessels.

The contractile effect of neuropeptide Y (NPY) was tested on isolated segments of basilar artery, central ear artery, gastro-epiploic artery and vein, and femoral artery and vein from the rabbit. At 30 nM NPY did not evoke vasoconstriction; at 300 nM NPY evoked a weak and variable response. NPY greatly potentiated the response of the gastro-epiploic and femoral arteries to noradrenaline without affecting the maximum response. As tested on the gastro-epiploic artery NPY was effective at concentrations of 1 nM and higher. As tested on the femoral artery the potentiating effect of 30 nM NPY on noradrenaline-evoked contractions was apparent immediately and 30 min after the application of NPY, but not after one hour. NPY (30 nM) potentiated the contractile response to noradrenaline and histamine but not to 5-hydroxytryptamine or high K+. The response to histamine was augmented in both arteries and veins, whereas the response to noradrenaline was enhanced in arteries but not in veins. NPY failed to potentiate the prostaglandin F2 alpha-evoked contraction except in the gastro-epiploic vein.

Animals↗
PubMed1983

Neuronal histamine in the gut wall releasable by gastrin and cholecystokinin.

Histamine accumulated in the ligated vagus nerve of the rat, both above and below the ligature; maximum accumulation was after 4 h. The finding is suggestive of axonal flow. Further evidence for histamine in peripheral nerves was obtained in experiments showing that the guinea-pig gut wall could be labelled with [3H]histamine. The experiments were carried out with isolated strips of stomach wall and taenia coli. Electrical stimulation released [3H]histamine from these specimens. The release could be blocked by Ca2+-free medium or by tetrodotoxin. The release was unaffected by vagal denervation or chemical sympathectomy (6-hydroxydopamine) but prevented by reserpinization. Gastrin-17 and cholecystokinin-39 released radioactivity by a tetrodotoxin-sensitive mechanism. The possible existence of a gastrin/cholecystokinin-sensitive neuronal pool of histamine in the gut wall offers a new perspective on the postulated role of histamine as a physiological stimulant of gastric acid secretion and might explain why H2-receptor antagonists block gastrin-stimulated acid secretion.

Animals↗
PubMed1982

Supersensitivity to substance P and physalaemin in rat salivary glands after denervation or decentralization.

Substance P, a putative neurotransmitter in mammals, and physalaemin, present in the skin of an amphibian, are both undecapeptides and belong to the family of tachykinins. The secretory effect of these tachykinins on parotid and submaxillary glands of the rat was examined. Dose-response curves showed that in the unoperated glands maximal secretory responses were obtained to an intravenous dose of 5-10 micrograms/kg of the tachykinins, that the amount of saliva secreted from the submaxillary gland was twice that from the parotid gland, and that physalaemin was more potent than substance P. Parasympathetic denervation of the parotid gland and decentralization of the submaxillary gland caused a marked sensitization to the tachykinins, as judged by lowered threshold doses for secretion and increased secretory responses to a series of submaximal doses 3 weeks postoperatively. Sensitization was less marked after sympathetic denervation and decentralization; in the parotid gland decentralization caused, in fact, no sensitization while in the submaxillary gland the degree of sensitization was about the same after the two types of operation. The tachykinins acted directly on the gland cells and the effect was not exerted via cholinergic, alpha-adrenergic or beta-adrenergic receptors. The pattern of sensitization to the tachykinins, found in the present study, after the different types of operation is similar to that previously found to cholinergic and alpha-adrenergic agonists and different from that to a beta-adrenergic agonist. Studies by others have shown that in the rat parotid gland peptidergic receptors share a common intracellular pathway with cholinergic and alpha-adrenergic receptors, whereas beta-adrenergic receptors use another pathway. In the present study it is suggested that this intracellular arrangement is of importance for the development of supersensitivity.

Adrenergic alpha-Agonists↗
PubMedDate not supplied

Mitogenic effect of neuropeptide Y in rat vascular smooth muscle cells.

Neuropeptide Y (NPY) is a vasoconstrictor released with norepinephrine from perivascular sympathetic nerves. Since sympathetic nerves appear to play a role in vascular smooth muscle cell (SMC) hypertrophy, we studied the effects of NPY on proliferation of cultured rat aorta- and vena cava-derived SMC. Both cell types displayed high-affinity NPY binding sites with displacement characteristics of [Pro34]NPY > NPY(13-36) > NPY(18-36) in aorta and [Pro34]NPY = NPY(13-36) = NPY(18-36) in the vena cava. Incubation with NPY (50-1000 nM) for 48 h increased by up to twofold cell number and [3H]-thymidine incorporation in both cell types (aortic more sensitive to NPY than venous). Following incubation with NPY, the disappearance of NPY immunoreactivity (-IR) from media was markedly delayed in the presence of SMC, and cell content of NPY-IR increased in a dose-dependent manner, indicating that SMC either diminish degradation of the peptide (possibly by internalization) or secrete endogenous NPY (or both). Structure-activity relationship studies with NPY(18-36) indicated involvement of Y1 receptors in mitogenesis. Thus, NPY has a mitogenic effect (probably mediated by Y1 receptors) and, therefore, may be a sympathetic trophic factor involved in vascular hypertrophy.

Animals↗
PubMedDate not supplied

Vascular effects of proteinase-activated receptor 2 agonist peptide.

Proteinase-activated receptor 2 (PAR-2) is a G protein-coupled receptor related to the thrombin receptor. PAR-2 can be activated by trypsin and by synthetic peptides corresponding to the new amino terminus generated by activating proteolytic cleavage. We show in this report that intravenous injection of PAR-2 agonist peptides has dramatic effects on arterial blood pressure in anesthetized rats. The peptide SLIGRLETQPPI, at 150 nmol/kg, transiently decreased the mean arterial pressure from 104 to 60 mm Hg. The hypotensive response was dose-dependent, and was not secondary to effects on central vasoregulatory systems, heart rate, or the kidneys. A nitric oxide synthase inhibitor attenuated the hypotensive response induced by the PAR-2 agonist peptide. Further experiments in vitro, on preparations of rat femoral artery and vein, showed that PAR-2 agonist peptide elicited a dose-dependent relaxation of both types of vessel. Removal of the endothelium abolished the agonist peptide-induced relaxation. Our results demonstrate that activation of PAR-2 can modulate vascular tone, and that this response was an effect mediated at least partly by nitric oxide. The effect on blood vessels further suggests that the physiological activator of this proteolytically activated receptor is an enzyme present and active in the blood, possibly after a vascular injury.

Amino Acid Sequence↗