| 1. |
- Dyakonova, V. E., et al.
(författare)
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Complex avoidance behavior and its neurochemical regulation in the land snail Cepea numerals
- 1995
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Ingår i: General Pharamacology. - 0306-3623. ; 26, s. 773-777
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Tidskriftsartikel (refereegranskat)abstract
- .1. In hot plate experiments, the pulmonate land snail Cepaea nemoralis displays a biphasic passive/active avoidance behaviour composed of retraction and subsequent searching mediated by antagonistic muscular systems. The switch, between the behaviours, is under neuronal control.2.2. Leu- and met-enkephalin, as well as FMRFamide-antiserum, attenuated the retraction response and potentiated the searching behaviour. Opposite effects were achieved by injection of antisera to the enkephalins.3.3. Both retraction and searching behaviours were potentiated by 5-HT. Methysergide antagonized the effects of the enkephalins on the searching behaviour.4.4. We conclude that endogenous opioids act antagonistic to FMRFamide in the neuronally controlled switch between passive and active avoidance behaviour.
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| 2. |
- Erlinge, David
(författare)
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Extracellular ATP: a growth factor for vascular smooth muscle cells
- 1998
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Ingår i: General Pharamacology. - 0306-3623. ; 31:1, s. 1-8
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Forskningsöversikt (refereegranskat)abstract
- 1. Extracellular adenosine triphosphate (ATP) is mitogenic for vascular smooth muscle cells (VSMC) and stimulates several events that are important for cell proliferation: DNA synthesis, protein synthesis, increase of cell number, immediate early genes, cell-cycle progression, and tyrosine phosphorylation. 2. Receptor characterization indicates mitogenic effects of both P2U and P2Y receptors. The P2X receptor is lost in cultured VSMC and is not involved. Several related biological substances such as UTP, ITP, GTP, AP4A, ADP, and UDP are also mitogenic. 3. Signal transduction is mediated via Gq-proteins, phospholipase C beta, phospholipase D, diacyl glycerol, protein kinase C alpha, delta, Raf-1, MEK, and MAPK. 4. ATP acts synergistically with polypeptide growth factors (PDGF, bFGF, IGF-1, EGF, insulin) and growth factors acting via G-protein-coupled receptors (noradrenaline, neuropeptide Y, 5-hydroxytryptamine, angiotensin II, endothelin-1). 5. The mitogenic effects have been demonstrated in rat, porcine, and bovine VSMC and cells from human coronary arteries, aorta, and subcutaneous arteries and veins. 6. The trophic effects on VSMC and the abundant sources for extracellular ATP in the vessel wall make a pathophysiological role probable in the development of atherosclerosis, neointima-formation after angioplasty, and possibly hypertension.
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| 3. |
- Grundemar, L, et al.
(författare)
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Multiple neuropeptide Y receptors are involved in cardiovascular regulation. Peripheral and central mechanisms
- 1993
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Ingår i: General Pharamacology. - : Elsevier BV. - 0306-3623. ; 24:4, s. 785-796
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Forskningsöversikt (refereegranskat)abstract
- 1. Neuropeptide Y (NPY) occurs in both the central and peripheral nervous system. In the periphery, NPY coexists with noradrenaline (NA) in perivascular sympathetic fibers. 2. NPY has a vasopressor effect, reflecting direct vasoconstriction of blood vessels and potentiation of the NA-evoked response. NPY also suppresses the release of NA from sympathetic fibers. 3. The post- and pre-junctional NPY receptors are referred to as Y1 and Y2, respectively. They recognize not only NPY but also the homologous gut hormone peptide YY (PYY). 4. The Y1 and Y2 receptors have been characterized in numerous test systems using analogs of NPY/PYY. Already the deletion of the first N-terminal amino acid (NPY 2-36) results in a marked loss of potency at the Y1 receptor. The Y2 receptor is much less dependent upon an intact N-terminus, and a wide range of C-terminal NPY fragments retain quite high potency. 5. Recently, yet another NPY receptor, Y3, that is distinct from Y1 and Y2 in that it recognizes PYY poorly, has been demonstrated in the brainstem and in the periphery. 6. Further attempts to characterize the various receptor types have relied on truncated and substituted analogs of NPY/PYY. Although such studies suggest the existence of at least three types of NPY receptors, the lack of antagonists has represented a problem. 7. Since NPY may regulate cardiovascular functions via peripheral and central receptors its physiological and possibly pathophysiological significance has attracted much attention. 8. The responsiveness to NPY seems to be altered in animal models of hypertension and elevated plasma levels of NPY have been found in patients under various conditions of stress and in primary hypertension. A number of studies have suggested that NPY may be a pathogenetic factor behind primary hypertension. 9. Antagonists for the various NPY receptors would be useful for an analysis of which effects of these peptides are physiologically relevant. It is tempting to predict that both agonists and antagonists of the NPY receptors could be useful as drugs, for instance, in the treatment of primary hypertension.
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| 4. |
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| 5. |
- Fredholm, BB
(författare)
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Purines and neutrophil leukocytes
- 1997
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Ingår i: General pharmacology. - : Elsevier BV. - 0306-3623. ; 28:3, s. 345-350
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Tidskriftsartikel (refereegranskat)
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| 6. |
- Garcia-Pascual, A, et al.
(författare)
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Endothelin-1-induced phosphoinositide hydrolysis and contraction in isolated rabbit detrusor and urethral smooth muscle
- 1993
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Ingår i: General Pharmacology. - 0306-3623 .- 1879-0011. ; 24:1, s. 131-138
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Tidskriftsartikel (refereegranskat)abstract
- 1. Endothelin-1 (ET-1) caused a concentration-dependent increase in the formation of inositol phosphates (IPs) in isolated rabbit detrusor and urethral smooth muscle preparations prelabelled with myo-[H-3]inositol. 2. The increase in accumulation of IPs was slow in onset in both detrusor and urethra, with no significant accumulation demonstrable during the first 30 min. The increase in IPs accumulation found after exposure of detrusor tissue to ET-1 (10(-7) M) for 2 hr (250 +/- 38%, n = 7) was not significantly different from that found in the urethra (279 +/- 40%, n = 6), when expressed as per cent of corresponding control values. 3. Pretreatment with nifedipine (10(-6) M) did not reduce IPs formation. In contrast, no increase in IPs formation was demonstrated in Ca2+-free medium. 4. ET-1 (10(-11) - 10(-7) M) produced concentration-dependent, slowly developing contractions in both detrusor and urethral preparations. Pretreatment with H-7 (3 x 10(-5) M) for 30 min before ET-1 application resulted in a non-parallel shift of the ET-1 concentration-response curve with significant reductions in maximal responses in both tissues. 5. ET-1-induced contractions in urethral preparations were markedly inhibited by Ni2+ (3 x 10(-4) M), whereas the effect of Ni2+ in the detrusor was less pronounced. 6. The results suggest that ET-1 stimulates phosphoinositide hydrolysis in the rabbit detrusor and urethra. Both IPs formation and contractile activation evoked by ET-1 are dependent on extracellular Ca2+. Ca2+-entry pathways seem to be differently activated in the detrusor and urethra, since Ca2+-influx through dihydropyridine-sensitive channels is involved in the ET-1-induced contraction of the detrusor, whereas a Ni2+-sensitive, nifedipine-resistant pathway seems to dominate in the urethra.
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| 7. |
- Bondeson, J, et al.
(författare)
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Antimalarial drugs inhibit phospholipase A2 activation and induction of interleukin 1beta and tumor necrosis factor alpha in macrophages
- 1998
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Ingår i: General Pharamacology. - 0306-3623. ; 30:3, s. 66-357
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Tidskriftsartikel (refereegranskat)abstract
- 1. The effects of antimalarial drugs on the intracellular signaling leading to activation of the phospholipase C and phospholipase A2 pathways and the induction of proinflammatory cytokines have been studied in mouse macrophages. 2. Both chloroquine and quinacrine, and to a lesser extent hydroxychloroquine, inhibited arachidonate release and eicosanoid formation induced by phorbol diester. This inhibition was due to that of the activation of the arachidonate-mobilizing phospholipase A2. 3. All three antimalarials potently inhibited arachidonate release induced by zymosan. They also inhibited the zymosan-induced formation of inositol phosphates, which hints that an inhibitory effect at the phospholipase C level might explain the inhibition of the response to zymosan. 4. Quinacrine, and to a lesser extent chloroquine, has an inhibitory effect on the lipopolysaccharide- or zymosan-induced expression of interleukin 1beta and tumor necrosis factor alpha, both at the mRNA and protein levels. This, in particular, has important implications for the mode of action of these compounds in rheumatoid arthritis.
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