The power of planning births.
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Birth Intervals↗
Biomedical subjects
P Adamson
Publications and source records attributed to P Adamson.
Kainate and quisqualate effects on rat presynaptic cortical receptors are metabotropic and non-additive.
The effects of quisqualate and kainate on synaptosomal inositol phosphate (InsP) labelling, 45Ca influx and intrasynaptosomal free calcium ([Ca2+]i) were investigated. Each agonist caused a concentration-dependent increase in both [Ca2+]i and InsP labelling: quisqualate, however, produced significantly larger responses in both parameters and at lower EC50 values. Neither quisqualate or kainate significantly affected 45Ca influx into synaptosomes, indicating that the observed increases in [Ca2+]i were due to mobilisation from intracellular stores. The concentration-dependent increases in [Ca2+]i promoted by quisqualate and kainate were monophasic, whereas the increases in InsP formation fitted well to a biphasic curve. The EC50 values suggest that both kainate and quisqualate initially mobilise calcium from inositol 1,4,5-trisphosphate (Ins 1,4,5-P3)-sensitive stores and that the resultant increases in [Ca2+]i will, above a certain threshold, promote further increases in InsP production by stimulation of Ca(2+)-dependent phospholipase C. When saturating concentrations of kainate and quisqualate were used in combination, the effects on both InsP labelling and [Ca2+]i were not additive but were slightly higher than those produced by kainate alone: combined administration of the two agonists had no effect on 45Ca influx. These results suggest that kainate acts as a partial agonist at the presynaptic quisqualate metabotropic glutamatergic receptor.
Animals↗
The kappa-opiate agonist U50488H decreases the entry of 45Ca into rat cortical synaptosomes by inhibiting N- but not L-type calcium channels.
The selective kappa-opiate agonist U50488H (1-100 microM) significantly reduced the uptake of 45Ca into cortical synaptosomes from the brain of the rat, in a time- and dose-dependent manner. In physiological medium, the maximum inhibition occurred after 2 min; this was approximately 55% (at 100 microM) and the IC50 was 80 nM. Nifedipine (1 microM) had no significant effect on the influx of Ca2+ in physiological medium (containing 5 mM K+), though, in fact, there was an approximately 20% decrease in the presence of 100 microM of drug. Nifedipine, however, did cause a significant blockade of the entry of 45Ca in medium containing 10 or 15 mM K+, demonstrating that L-type channels on synaptosomes were operational under depolarising conditions. Under these depolarising conditions, there was an additive inhibitory effect on entry of 45Ca into synaptosomes when U50488H (1 microM) and nifedipine (1 microM) were incubated together. Treatment of synaptosomes with omega-conotoxin (omega-CgTx, 0.5 microM) resulted in a 35% reduction in the uptake of 45Ca. omega-Conotoxin (0.5 microM) or naloxone (20 microM) abolished the inhibitory effect of U50488H on the uptake of 45Ca, but naloxone did not alter the blockade of L-type Ca2+ channels, caused by nifedipine. In conclusion, the data demonstrate that under depolarising conditions, there are functional L-type calcium channels on nerve endings in the CNS.(ABSTRACT TRUNCATED AT 250 WORDS)
3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
Presynaptic glutamate/quisqualate receptors: effects on synaptosomal free calcium concentrations.
Intracellular free [Ca2+]i was measured using fura-2 in synaptosomes prepared from cerebral cortices of adult male rats (12 weeks). L-(+)-Glutamate, D-(-)-glutamate, and quisqualate produced similar dose-dependent increases in [Ca2+]i, with EC50 values of 0.38 microM, 0.74 microM, and 0.1 microM, respectively, and maximum increases of approximately 40%. Ibotenate showed less affinity (EC50 4.4 microM) but had a greater maximum effect (57%). N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) did not increase [Ca2+]i. The increases in [Ca2+]i induced by quisqualate and ibotenate were not diminished in the absence of extrasynaptosomal Ca2+. L-2-Amino-4-phosphonobutyrate (L-AP4) (1 microM) completely blocked the changes in [Ca2+]i induced by L-(+)-glutamate, D-(-)-glutamate, quisqualate, or ibotenate. The effects of quisqualate and ibotenate on [Ca2+]i were also blocked by coincubation of synaptosomes with L-(+)-serine-O-phosphate (L-SP) (1 mM) (which, like L-AP4, blocks the effects of quisqualate and ibotenate on inositol phospholipid metabolism). 6-Cyano-7-nitroquinoxaline-2,3-dione (CNQX) had no effect on agonist-mediated increases in [Ca2+]i when coincubated with either quisqualate or ibotenate. These data are consistent with the existence of presynaptic glutamate receptors (of the excitatory amino acid metabotropic type) which activate phospholipase C leading to the elevation of inositol 1,4,5-trisphosphate and release of Ca2+ from intracellular stores.
6-Cyano-7-nitroquinoxaline-2,3-dione↗
The effect of cosmetic rhinoplasty on nasal patency.
Fifty patients who primarily desired cosmetic improvement underwent nasal airflow studies using posterior rhinomanometry before and after reduction rhinoplasty. There was no significant difference in nasal resistance before and after surgery. This study demonstrates that neither subjective nor objective nasal obstruction follows reduction rhinoplasty, despite the potential for a decreased cross-sectional area of the valve region.
Adult↗
Increased angiogenesis during wound healing in rats with streptozotocin-diabetes.
The neovascularization that occurs during wound healing in the perforated mesenteric membrane was quantitatively studied in rats with streptozotocin induced diabetes. The virtually avascular mesenteric windows in both controls and diabetic rats were perforated with a scalpel during laparatomy. At designated intervals during days 1-63 postoperatively, the mesenteries were excised, fixed, and cut perpendicularly through the wound margin or the central part of a closed wound. An unperforated window from each animal served as an internal control. The numerical microvascular density of the healing tissue and the unperforated control mesentery was assessed by morphometry on photomicrographs with regard to number of vascular profiles per mm length of mesentery or mm2 sectioned tissue area. The vascularity in unperforated windows of both diabetics and age-matched healthy controls was unaffected by laparotomy whereas perforation significantly increased the numerical microvascular density of the mesentery. The onset of angiogenesis in the perforated mesenteries occurred on days 5-7 and in both diabetics and controls, wound areas retained an increased numerical microvascular density throughout the observation period. The numerical microvascular density of the wound areas was greater in diabetics than controls following closure of the wounds. A number of wounds healed without being vascularized. The number of vascularized wounds was significantly higher in diabetic animals than controls.
Animals↗
Presynaptic alpha 2-adrenoceptor and kappa-opiate receptor occupancy promotes closure of neuronal (N-type) calcium channels.
Synaptosomes prepared from rat cerebral cortex by homogenization in isotonic sucrose and centrifugation on four-step discontinuous percoll density gradients were loaded with the fluorescent indicator fura-2 to allow measurement of intrasynaptosomal free calcium concentrations [( Ca2+]i). Incubation of fura-2 loaded synaptosomes with either the kappa-opiate agonist U-50,488H (0.1-100 microM) or the alpha 2-adrenoceptor agonist clonidine (0.1-100 microM), resulted in a dose-dependent reduction in [Ca2+]i and these changes were completely antagonised by prior inclusion of naloxone (20 microM) or idazoxan (RX781094) (2 microM) respectively. When the 1,4-dihydropyridine Ca2+-channel blocker nifedipine (1 microM) was incubated with synaptosomes for 1 min, there was a 17.0% decrease in [Ca2+]i and when it was combined with either U-50,488H (1 microM) or clonidine (1 microM) there was a reduction in [Ca2+]i of 35.0 and 48.1% respectively i.e. the effects were additive. The increases in the depression of [Ca2+]i produced by these drug combinations were antagonised by the inclusion of naloxone (20 microM) or idazoxan (2 microM) which resulted in decreases in free [Ca2+]i of 26.5 and 14.1% respectively. These data indicate that the effects of clonidine and U-50,488H are not mediated by L-type Ca2+ channels.(ABSTRACT TRUNCATED AT 250 WORDS)
3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
Intrasynaptosomal free calcium concentration is increased by phorbol esters via a 1,4-dihydropyridine-sensitive (L-type) Ca2+ channel.
Incubation of non-depolarised fura-2-loaded rat cortical synaptosomes with 12-tetradecanoylphorbol-13-monoacetate (TPA) results in a dose-dependent increase in calcium concentration (to a maximum of 140%). It is dependent on extrasynaptosomal Ca2+, is partially blocked by 1 microM verapamil and effectively blocked by 100 microM verapamil (greater than or equal to 90%). Nifedipine (1 microM), nicardipine (1 microM) and omega-conotoxin fraction GVIA from Conus geographus (50 nM) (omega-CgTx) also cause blockade (greater than or equal to 90%) of the increase. The sensitivity of the TPA-induced increase in calcium concentration to omega-CgTx, nicardipine and nifedipine, but not to low concentrations of verapamil (1 microM), suggests that the TPA-induced rise in calcium concentration is mediated by increased Ca2+ influx through 1,4-dihydropyridine-sensitive Ca2+ channels. Incubation of synaptosomes with the inactive phorbol ester phorbol-13-monoacetate (TMA) does not result in any significant dose-dependent increase in calcium concentration. The data which are presented are consistent with (i) the proposal that phorbol ester-induced increases in calcium concentration are the result of Ca2+ influx through an L-type Ca2+ channel and (ii) the existence of functioning L-type Ca2+ channels on rat brain synaptosomes.
Animals↗
Alpha 2-adrenergic, kappa-opiate, and P1-purinergic autoreceptors have mutually antagonistic effects: a new regulatory mechanism?
Rat cortical synaptosomes prepared on four-step discontinuous Percoll density gradients were loaded with the fluorescent Ca2+-indicator fura-2 to allow measurement of the intrasynaptosomal free calcium concentration ([Ca2+]i). When P1-purinergic, alpha 2-adrenergic, or kappa-opiate agonists were incubated with these synaptosomes for 1 min, there was a highly significant, dose-dependent reduction in [Ca2+]i. The effects of these agonists were blocked by inclusion of appropriate specific antagonists. When alpha 2-adrenergic and P1-purinergic agonists were coincubated, a mutual antagonism of their effects was observed, and, in fact, an increase rather than a decrease in [Ca2+]i was apparent. This mutual antagonism was reversed by addition of either a P1-purinergic or a alpha 2-adrenergic antagonist. Parallel studies in which kappa-opiate and P1-purinergic agonists were coincubated also demonstrated a mutual antagonism between the individual effects that was reversed by prior inclusion of either a kappa-opiate or P1-purinergic antagonist. As these mutually antagonistic effects have been observed between alpha 2-adrenergic, kappa-opiate, and P1-purinergic receptor-mediated events, we suggest that this may be a general phenomenon and may be a regulatory mechanism at nerve endings.
3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
Cyclic AMP analogues potentiate kappa-opiate and attenuate alpha 2-adrenoceptor agonist effects on intrasynaptosomal free calcium.
The intrasynaptosomal free calcium concentration ([Ca2+]i) was measured in quin2-loaded synaptosomes prepared from rat cerebral cortex. Membrane-permeant cyclic adenosine-3',5'-monophosphate (cAMP) analogues [8-bromo-cyclic adenosine-3',5'-monophosphate (8-Br-cAMP) and dibutyryl-cyclic adenosine-3',5'-monophosphate (db-cAMP)] increased [Ca2+]i in a dose-dependent manner; The maximal increases were approximately 50% for 8-Br-cAMP and 35% for db-cAMP and occurred at approximately 10 microM with both analogues. Clonidine (1 microM) alone reduced [Ca2+]i by 26.5%; db-cAMP and 8-Br-cAMP attenuated this reduction to 14.2 and 8.2%, respectively. In contrast, the reduction (19.9%) in [Ca2+]i induced by the preferential kappa-opiate agonist dynorphin A(1-13) was not attenuated by the cAMP analogues; in fact, db-cAMP and 8-Br-cAMP potentiated the effect of dynorphin A(1-13) (1 microM), producing decreases in [Ca2+]i of 33.6 and 29.6%, respectively. We conclude that although alpha 2-adrenergic and kappa-opiate receptors both reduce [Ca2+]i, the alpha 2-adrenoceptor-mediated response and the kappa-opiate receptor-mediated response involve different effector mechanisms. It appears that presynaptic alpha 2-adrenoceptor agonist effects are linked to reductions in adenylate cyclase activity and cAMP production and a resultant increase in Ca2+ sequestration, Ca2+-channel blockade, or both. On the other hand, the kappa-opiate-mediated effects possibly involve an increase in cAMP production and a blockade of Ca2+ entry.
Adrenergic alpha-Agonists↗
Mutual antagonism of kappa-opiate and alpha 2-adrenoceptor agonist effects on intrasynaptosomal free [Ca2+]i.
Synaptosomes prepared from rat cerebral cortices on Percoll discontinuous density gradients were loaded with the fluorescent EGTA analogue Quin 2 to allow measurement of intracellular free [Ca2+]i. When either kappa-opiate or alpha 2-adrenoceptor agonists were incubated with the synaptosomes, there was a highly significant (p less than 0.004, p less than 2.7 X 10(-6), respectively) reduction in intrasynaptosomal free [Ca2+]i relative to controls. As these synaptosomes are not depolarised, the data suggest that both alpha 2-adrenoceptor agonists and kappa-opiate agonists inhibit neurotransmitter release, decreasing the availability of intraneuronal [Ca2+]i rather than altering Ca2+ entry. However, when these two agonists were coincubated, there was a complete abolition of the effects of either agonist; in fact, there was an apparent increase in the intrasynaptosomal free [Ca2+]i. Neither morphine nor [D-Ala2-D-Leu5]enkephalin, mu and delta opiate agonists respectively, had any significant effect on intrasynaptosomal free [Ca2+]i. These results show that the individual effects of clonidine and dynorphin A1-13 are in keeping with the role of these substances at autoreceptors controlling neurotransmitter release. The mutual antagonism of their effects on [Ca2+]i is more difficult to explain but it may be a mechanism that prevents the occurrence of excessive inhibition of neuronal systems.
Aminoquinolines↗
Synaptosomal free [Ca2+] is reduced by clonidine and dynorphin A-(1-13) and increased by idazoxan.
Intrasynaptosomal free calcium concentrations measured in rat cortical synaptosomes using the calcium sensitive fluorescent dye quin 2, were found to be 0.107-0.122 microM (n = 33). Stimulation of alpha 2-adrenoceptors or kappa-opiate receptors with clonidine (0.1-100 microM) or dynorphin A fragment (1-13) (0.2-5.0 microM) respectively, produced a dose dependent reduction in the intrasynaptosomal free calcium concentration. The alpha 2-adrenoceptor mediated reduction produced by clonidine (100 microM) was antagonised by the selective alpha 2-antagonist idazoxan (RX781094) (200 microM). Dynorphin A-(1-13) (1 microM) caused a reduction which was antagonised by a high (20 microM) but not low (2.0 microM) concentration of naloxone. We conclude that unlike the mu- and delta-opiate receptor, stimulation of alpha 2-adrenoceptors or kappa-opiate receptors elicits changes in intrasynaptosomal free calcium concentration which are independent of the voltage sensitive calcium channel. This does not preclude the possibility that the alpha 2-adrenoceptor and kappa-opiate receptor also have an effect at the voltage sensitive calcium channel.
Adrenergic alpha-Antagonists↗
Radiation effects on mast cells: secretory ability, histamine release and recovery, and cell number.
We studied the effects of irradiation with a single fraction of high-energy electrons, in the absorbed dose range used in radiotherapy, on features related to the rat mesenteric mast-cell (MC) population. Such features were energy dispersive X-ray microanalysis for zinc, light and transmission electron microscopic changes, histamine content, and secretory ability of MCs when exposed to the potent secretagogue 48/80. The observation period was 14 days. Also studied were the effects of radiation on the number and histamine content of free peritoneal MCs. Irradiation-induced decrease in histamine content was delayed for at least two days and the rate of subsequent recovery of mesenteric histamine was approximately 70% below normal. This was corroborated by the findings of necrotic and fragmented mesenteric MCs during the entire experimental period. Fibroblasts and macrophages phagocytosed groups of MC granules as well as individual MC granules. A fraction of the extruded MC granules retained an almost normal appearance. This suggests that they were solubilized unduly slow presumably because the irradiation destroyed the mechanisms and enzymes which normally degrade the heparin-protein granule matrix and its heparin. Moreover, the irradiation suppressed the secretory ability of mesenteric MCs and significantly reduced the number of free peritoneal MCs. The findings indicate that the MC is a remarkably radiosensitive connective-tissue cell.
Animals↗
A population policy and a development policy are one and the same thing. An introduction to World Population Year.
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Demography↗
Open rhinoplasty: an assessment.
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Humans↗