Pearl Harbor and the Emperor's physiologists.
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Climate↗
Biomedical subjects
J Diamond
Publications and source records attributed to J Diamond.
Lack of correlation between activation of cyclic AMP-dependent protein kinase and inhibition of contraction of rat vas deferens by cyclic AMP analogs.
The effects of N6,O2-dibutyrl-adenosine-3',5'-cyclic monophosphate (db-cAMP) and 8-bromo-adenosine-3',5'-cyclic monophosphate (8-Br-cAMP) on tension and cAMP-dependent protein kinase (PKA) activities in rat vas deferens were investigated. A soluble enzyme fraction obtained from the vas deferens was found to contain both type I and type II isozymes of PKA, whereas a particulate fraction contained only the type II isozyme. Exposure of the vas deferens to db-cAMP (1-100 microM) for 30 min caused a concentration-dependent inhibition of phenylephrine-induced contractions, with an EC50 of less than 10 microM. 8-Br-cAMP had no significant effect on contractions over a similar concentration range. Both of the analogs were able to activate PKA significantly at a concentration of 10 microM, and the magnitude of the PKA activation was greater with 8-Br-cAMP than with db-cAMP. Charcoal was added to the homogenization buffer in these experiments to prevent the artifactual activation of PKA by cAMP analogs trapped in the extracellular space. The ability of db-cAMP, but not 8-Br-cAMP, to inhibit the contraction of vas deferens could not be explained on the basis of differential activation of soluble or particulate PKA or of specific isozymes of the enzyme. It is, therefore, concluded that activation of PKA is not responsible for the relaxant effects of cAMP analogs in some smooth muscle.
8-Bromo Cyclic Adenosine Monophosphate↗
The effect of phenylephrine on inositol 1,4,5-trisphosphate levels in vascular smooth muscle measured using a protein binding assay system.
This study utilizes a protein binding assay system to evaluate agonist-induced changes in inositol 1,4,5-trisphosphate (IP3) in rat aorta. Phenylephrine induced a rapid transient increase in IP3 content of rat aorta which was concentration dependent and blocked by prazosin. The concentration response curve to IP3 formation was shifted to the right of the concentration-response curve for contraction in normal calcium-containing buffer but was close to that obtained in calcium-free medium. This suggests that although IP3 may play an important role in mediating release of intracellular Ca2+, other factors (e.g. Ca2(+)-influx) may be involved in determining the magnitude of vascular smooth muscle contraction in Ca2(+)-containing solutions. Both 8-bromo cyclic GMP and sodium nitroprusside significantly attenuated the phenylephrine-induced IP3 formation. Removal of the endothelium did not alter the generation of IP3.
Animals↗
Partial characterization of cyclic AMP-dependent protein kinases in guinea-pig lung employing the synthetic heptapeptide substrate, kemptide. In vitro sensitivity of the soluble enzyme to isoprenaline, forskolin, methacholine and leukotriene D4.
This paper describes the partial characterization of soluble cyclic AMP-dependent protein kinase (A-kinase) in guinea-pig lung using Kemptide, a synthetic serine-containing heptapeptide, and examines the sensitivity of this enzyme to drugs which are reported to increase and to decrease the intracellular concentration of cyclic AMP. Differential centrifugation of lung homogenates revealed that 78% of A-kinase was present in the 31,000 gmax x 15 min supernatant fraction. Both basal and cyclic AMP-stimulated phosphotransferase activity of this 'soluble' enzyme were abolished by the heat-stable inhibitor of A-kinase. Soluble A-kinase was Mg2(+)-dependent (apparent Km and and Kact 8.6 and 2.6 mM, respectively) and was stimulated nine-fold by saturating concentrations of both cyclic AMP (Kact: 131 nM) and cyclic GMP (Kact: 28.7 microM) at a protein (enzyme) concentration of 1.3 micrograms. Kinetic analysis of the effect of Kemptide and ATP revealed linear, Hanes plots with Michealis constants of ca. 12 and 13 microM, respectively. Chromatography of the soluble enzyme over DEAE-cellulose resolved three peaks of catalytic activity when fractions were assayed in the presence of cyclic AMP (10 microM): (i) free catalytic subunits (5%), (ii) Type I isoenzyme (5%) and (iii) Type II isoenzyme (90%). The A-kinase activity ratio was markedly increased in lung pre-treated with the smooth muscle relaxants isoprenaline and forskolin. This biochemical effect was both time- and concentration-dependent and was temporally associated with the ability of these drugs to reduce lung parenchymal tone. In contrast, the contractile agonists, methacholine (Mch) and leukotriene (LT) D4 exerted opposite effects on A-kinase activity. Thus, Mch significantly reduced cyclic AMP levels and lowered basal A-kinase activity whilst the converse was true for LTD4. For both drugs this biochemical effect accompanied contraction of the lung. Pre-treatment of lung tissue with flurbiprofen, an irreversible inhibitor of cyclo-oxygenase in vitro, abolished the ability of LTD4 to increase the A-kinase activity ratio suggesting that this biochemical response was mediated indirectly through the stimulated biosynthesis and release of a prostanoid(s) able to activate adenylyl cyclase; the increase in tension induced by LTD4, however, was not significantly affected by flurbiprofen pre-treatment. Collectively, these data support the concept that soluble A-kinase activity in guinea-pig lung can be regulated by changes in intracellular cyclic AMP and that activation and/or inhibition of this biochemical cascade may influence alterations in lung contractility.(ABSTRACT TRUNCATED AT 400 WORDS)
Adenosine Triphosphate↗
Evaluation of kemptide, a synthetic serine-containing heptapeptide, as a phosphate acceptor for the estimation of cyclic AMP-dependent protein kinase activity in respiratory tissues.
In the search for a phosphate acceptor to estimate cyclic AMP-dependent protein kinase (A-kinase) activity in respiratory tissues devoid of the disadvantages inherent with the use of histones, we compared and contrasted a conventional substrate, histone IIa, with that of a novel heptapeptide phosphate acceptor, Kemptide (Kemp et al., J Biol Chem 252: 4888-4894, 1977). The specific activities of soluble A-kinase isolated from guinea-pig lung parenchyma and from bovine tracheal smooth muscle were significantly (12-16-fold) greater when Kemptide was used as substrate when compared to histone IIa. Moreover, studies with a specific inhibitor of A-kinase demonstrated that whilst the cyclic AMP-stimulated phosphorylation of Kemptide was catalysed exclusively by A-kinase, only approximately 89% of the phosphate incorporated into histone IIa was attributed to the activity of this enzyme. The activation constant (Kact) of cyclic AMP for A-kinase was estimated to be 1.5 microM when Kemptide was used as substrate, 25-fold higher than that obtained using histone IIa (60 nM) under identical conditions. In a complementary series of experiments it was found that both the basal and isoprenaline-stimulated A-kinase activity ratios were significantly higher when histone IIa was used as substrate when compared with that obtained using Kemptide. Elevating the ionic strength of the homogenization buffer or assay cocktail with NaCl produced a reversible (following dialysis), concentration-dependent, mixed uncompetitive, inhibition of cyclic AMP-stimulated histone phosphorylation; phosphokemptide formation was unaffected. The ability of salt to inhibit A-kinase activity also affected the elution profile of A-kinase isoenzymes following their separation by DEAE-cellulose chromatography. With histone IIa as substrate the Type I:Type II isoenzyme ratio in guinea-pig lung and in bovine tracheal smooth muscle was 9:91 and 35:65, respectively. Changing the phosphate acceptor to Kemptide reduced these respective ratios to 5:95 and 29:71. Although the effect on the isoenzyme ratio was small, the specific activities of the two isoenzymes isolated from both tissues were markedly attentuated by ca. 9% (Type I) and 36% (Type II). It is concluded that Kemptide is without many of the disadvantages inherent with histone IIa and is, thus, a preferable phosphate acceptor for estimating soluble A-kinase activity and determining the isoenzyme ratio in guinea-pig lung and in bovine tracheal smooth muscle.
Animals↗
Sustained metabolic scope.
Sustained metabolic rates (SusMR) are time-averaged metabolic rates that are measured in free-ranging animals maintaining constant body mass over periods long enough that metabolism is fueled by food intake rather than by transient depletion of energy reserves. Many authors have suggested that SusMR of various wild animal species are only a few times resting (basal or standard) metabolic rates (RMR). We test this conclusion by analyzing all 37 species (humans, 31 other endothermic vertebrates, and 5 ectothermic vertebrates) for which SusMR and RMR had both been measured. For all species, the ratio of SusMR to RMR, which we term sustained metabolic scope, is less than 7; most values fall between 1.5 and 5. Some of these values, such as those for Tour de France cyclists and breeding birds, are surely close to sustainable metabolic ceilings for the species studied. That is, metabolic rates higher than 7 times RMR apparently cannot be sustained indefinitely. These observations pose several questions: whether the proximate physiological causes of metabolic ceilings reside in the digestive tract's ability to process food or in each tissue's metabolic capacity; whether ceiling values are independent of the mode of energy expenditure; whether ceilings are set by single limiting physiological capacities or by coadjusted clusters of capacities (symmorphosis); what the ultimate evolutionary causes of metabolic ceilings are; and how metabolic ceilings may limit animals' reproductive effort, foraging behavior, and geographic distribution.
Animals↗
The ACR Practice Accreditation Program for radiation oncology.
Quality assurance, an issue receiving great attention in medicine of late, has its origins in the consumerism of the mid 60's and in the budgetary problems which became more pronounced following the oil embargo of the 1970's. Consumerism, initially concerned with product safety, eventually extended to the patient/doctor relationship. Physicians became providers of healthcare, and as such were increasingly viewed as liable for the results of that care. A bad result implied bad care. The rate of malpractice claims began to increase, with a concomitant increase in malpractice insurance premiums. This upward pressure on medical costs came at a time of economic crisis, related in part to increasing oil costs, competition from foreign manufacturers, and rising national debt. It was inevitable, therefore, that those who pay for medical care (private insurers and the government) would look for ways to ensure that the care they were buying was both necessary and of good quality.
Accreditation↗
The neural dependency of Merkel cell development in the rat: the touch domes and foot pads contrasted.
We have used the quinacrine labeling technique and electron microscopy to study the development of the Merkel cell population in the skin of the rat and how this is affected by denervation produced at birth and at various times thereafter. An unexpected difference was found between the Merkel cells of glabrous and hairy skin. In the paw pads of rats aged 1 day or older the Merkel cells differentiated normally and survived quantitatively in the absence of their nerves. In the touch domes however, denervation at 1-4 days prevented the differentiation of the normal Merkel cell population and led to the disappearance of all or most of the Merkel cells that were already present. The Merkel cells in touch domes of the lower leg were affected by denervation like those of the back skin, differing strikingly from the Merkel cells of the footpads, even though the hairy skin of the leg and the glabrous skin of the foot are innervated by the same anatomical nerve. In adult rats, axons regenerating to denervated paws reinnervated epidermal Merkel cells of the pads and restored essentially normal mechanosensitivity to them; thus the Merkel cells of mammalian glabrous skin, like their counterparts in the wholly glabrous skin of lower vertebrates (S. A. Scott, E. Cooper, and J. Diamond, 1981, Proc. R. Soc. London B211, 455-470; K. M. Mearow and J. Diamond, 1988, Neuroscience 26, 695-708), can act as targets for ingrowing nerves. However, even though the differentiation of Merkel cells in hairy skin is nerve dependent, they probably have in common with the Merkel cells of glabrous skin the role of acting as final targets for nerves during development and regeneration.
Aging↗
The effect of M&B 22948 on methacholine- and histamine-induced contraction and inositol 1,4,5-trisphosphate levels in guinea-pig tracheal tissue.
The effect of a cyclic GMP phosphodiesterase inhibitor, M&B 22948, on methacholine- and histamine-induced contraction and inositol 1,4,5-trisphosphate (IP3) elevation was studied in guinea-pig tracheal rings. After addition of methacholine or histamine the rise in IP3 content was rapid and transient reaching a maximum after 5-15 s, which coincided with the maximum rate of tension development. Cyclic GMP levels of the tissue were elevated by M&B 22948 before agonist stimulation and further elevated by addition of methacholine or histamine. Cyclic AMP levels were not altered by any of these agents. M&B 22948 abolished IP3 generation induced by methacholine or histamine, but did not alter the rate or magnitude of tension development. Thus, IP3 generation does not appear to be responsible for the contractions induced by methacholine or histamine in this tissue.
3',5'-Cyclic-AMP Phosphodiesterases↗
Role of cGMP in relaxation of vascular and other smooth muscle.
The hypothesis that the relaxant action of many drugs on vascular and other smooth muscle is mediated by increases in intracellular cGMP, the "cGMP hypothesis," is gaining wide acceptance. While much information supporting this idea can be found in the literature, there is also a significant amount of information indicating that an elevation in the tissue content of cGMP is by itself insufficient to cause smooth muscle relaxation. The literature is reviewed with reference to the criteria that need to be fulfilled to consider cGMP as the second messenger mediating relaxation of smooth muscle by a drug; i.e., activation of guanylate cyclase, elevation of tissue content of cGMP, potentiation by phosphodiesterase inhibitors, antagonism by inhibitors of cGMP synthesis, and production of relaxation by cGMP analogues. For each criterion, key observations supporting the hypothesis are considered, followed by examples of important observations not consistent with the hypothesis. It is concluded that in some smooth muscles, for example, rat myometrium and vas deferens, cGMP is not a mediator of drug-induced relaxation. In other smooth muscles, including vascular smooth muscle, cGMP appears to play an important role in the relaxation process; but current evidence suggests that other factors are also important and that the cGMP hypothesis may need to be modified.
Animals↗
Axonal domains within shared touch domes in the rat: a comparison of their fate during conditions favoring collateral sprouting and following axonal regeneration.
Low-threshold mechanosensory nerves in the adult rat differ both from their counterparts in lower vertebrates and from high-threshold nociceptive nerves in mammals in that they appear not to undergo collateral sprouting into adjacent denervated skin, although they will clearly regenerate into it after they are damaged. We have now studied the growth capabilities of the low-threshold nerves supplying touch domes, the visible mechanosensory structures scattered throughout the hairy skin. Touch domes in the rat are often multiply innervated. A serendipitous observation on such domes allowed us to investigate the possibility that a functional collateral sprouting of their nerves can indeed occur, but only to a spatially very restricted extent, e.g., within the confines of a partially denervated dome. We used a "prodder" with a tip diameter of 16 micron to examine the mechanosensory profile across single domes that were preselected as being supplied by only two axons, one running in each of two adjacent dorsal cutaneous nerves (DCNs). Simultaneous recordings were made of the afferent discharges evoked in these nerves when the prodder was applied at about 17 or more locations on a selected dome; the spatial resolution was better than 55 micron. We found that within such a shared dome, one axon can supply a discrete territory (its "domain"), which may or may not overlap with the corresponding domain of the other axon. In a preliminary electron microscopic study, we found no evidence for a sharing of single Merkel cells, which are the specialized sensory cells in touch domes, even in the regions of a shared dome where two domains overlapped; each innervated Merkel cell appeared to be contacted by a single nerve ending, implying that in a shared dome each axon probably supplies an exclusive subpopulation of the Merkel cells. We tested for functional collateral sprouting by eliminating one nerve to a shared dome, and at a selected time thereafter mapping the domain of the remaining axon to see whether it had enlarged. The result was the same whether the two domains initially had a region of overlap or not; no expansion of the surviving domain occurred over postoperative periods up to 4 months (an expansion of the domain by 55 micron would have been detected). Thus functional collateral sprouting had failed to occur.(ABSTRACT TRUNCATED AT 400 WORDS)
Animals↗
Merkel cells and the mechanosensitivity of normal and regenerating nerves in Xenopus skin.
We have investigated some of the physiological, morphological and trophic characteristics of the Merkel cell-neurite complexes in the skin of Xenopus laevis. The Merkel cells, which are specialized sensory cells, occur in groups of 2-4 around the openings of the cutaneous gland ducts. A voltage-controlled mechanical stimulator was used to determine the distribution of mechanosensory thresholds across the skin; an analysis of the results revealed the presence of a single population of rapidly adapting, low threshold mechanoreceptors, whose locations coincided with those of the epidermal Merkel cell-neurite complexes. The possible role of the Merkel cell in the mechanosensory process, and its trophic interactions with the sensory nerve, were examined (i) by following the development of mechanosensitivity when sensory nerves regenerated into denervated, or newly regenerated, skin; (ii) by looking for possible correlations between the expression of physiological function and the appearance of morphological features characteristic of the Merkel cell-neurite complex; and (iii) by investigating the mechanosensitivity that remained after elimination of the Merkel cells. Not only did Merkel cells survive denervation without obvious changes in their fine structure, but they developed with normal morphology in new skin that had regenerated in nerve free limbs. Ingrowing sensory nerves contacted these Merkel cells, and eventually normal mechanosensory function was established; thus the Merkel cells act as targets for these nerves. The full recovery of the normal pattern of mechanosensitivity in the skin following nerve regeneration was correlated with the redevelopment of the specialized contacts between the nerve endings and Merkel cells, that eventually included reciprocal synapses. However, following the mechanical removal of the epidermis by enzymatic treatment, or the selective elimination of the Merkel cells by irradiation after they had taken up the fluorescent dye quinacrine, essentially normal mechanosensory responses could be initiated, though with somewhat increased thresholds. The results indicate that the Merkel cells are not involved in mechanosensory transduction; they do, however, act as targets for the growing nerves, thereby ensuring the appropriate distribution of low threshold mechanosensitivity, and they may have a role in enhancing and even inducing the excitability of the mechanosensitive nerve endings.
Animals↗
Evidence that the Merkel cell is not the transducer in the mechanosensory Merkel cell-neurite complex.
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Animals↗
Dietary regulation of intestinal transport of the dipeptide carnosine.
Uptake of the dipeptide L-carnosine was measured in everted intestinal sleeves of mice whose dietary protein level or else proportion of protein in the form of free amino acids was varied experimentally. Carnosine uptake was highest in the jejunum, regardless of ration. Compared with a low-protein (18%) ration, a high-protein (72%) ration stimulated carnosine uptake by 30-70% in duodenum and jejunum (but not in ileum). This stimulation was observed even in the presence of peptidase inhibitors that inhibit cell surface hydrolysis of dipeptides. Measured carnosine hydrolysis was low or negligible. Carnosine uptake was the same in mice fed 54% unhydrolyzed casein, 54% partly hydrolyzed casein, and 54% free amino acids formulated so as to stimulate a complete hydrolysate of casein. Thus carnosine uptake is regulated by dietary levels of amino acids, peptides, and proteins, all of which seem equally effective at inducing carnosine transporters.
Animals↗
Regulatory signals for intestinal amino acid transporters and peptidases.
Dietary protein ultimately regulates many processes involved in protein digestion, but it is often unclear whether proteins themselves, peptides, or amino acids (AAs) are the proximate regulatory signal. Hence we compared several processes involved in protein digestion in mice adapted to one of three rations, identical except for containing 54% of either casein, a partial hydrolysate of casein, or a free AA mixture simulating a complete hydrolysate of casein. We measured brush-border uptakes of seven AAs that variously serve as substrates for four AA transporters, and brush-border and cytosolic activities of four peptidases. The three rations yielded essentially the same AA uptake rates. Peptidase activities tended to be lower on the AA ration than on the protein ration. In other studies, all three rations yielded the same rates of brush-border peptide uptake; protein is only modestly more effective than AAs at inducing synthesis of pancreatic proteases; and, depending on the animal species, protein is either much less or much more effective than AAs at stimulating release of cholecystokinin and hence of pancreatic enzymes. Thus the regulators of each process involved in protein digestion are not necessarily that process's substrate. We call attention to other cases in which the functional significance of regulatory signals remains to be understood.
Amino Acids↗
Nociceptive cutaneous stimuli evoke localized contractions in a skeletal muscle.
1. The cutaneus trunci muscle (CTM) is a thin broad sheet of skeletal muscle that originates bilaterally on the humerus and inserts beneath the dermis of back and flank skin. A nociceptive stimulus applied to the skin elicits a localized reflex contraction in that region of the CTM underlying the site of sensory stimulation. While this "local sign" character of the CTM reflex corresponds to the segmental distribution of the afferent nerves (the dorsal cutaneous nerves, or DCNs) that enter the spinal cord in the lower thoracic and the lumbar levels, the motor output originates entirely from a circumscribed region of the cervical spinal cord. 2. Electrophysiological analysis of EMG activity in the muscle reflexly evoked by direct electrical stimulation of individual DCNs revealed a distinct topographic relationship, in that the shortest latency response of EMG activity in the muscle was consistently located approximately 1.0 cm rostral to the dermatome of the stimulated DCN. 3. Histochemical studies of the CTM show that individual muscle fibers run rostrocaudally, are focally innervated, and in adult rats, are approximately 3.0 cm in length. The major motor nerves exit from the brachial plexus, and functionally they divide the muscle into longitudinal (rostrocaudal) territories, which thus lie orthogonal to the dermatomal pattern of sensory innervation. The localized reflex responses to focal sensory stimuli indicate that the major longitudinal muscle fields contain many "reflex compartments." 4. The compartmentalized nature of the reflex response in the CTM suggests that nociceptive input from any one sensory dermatome has a preferred access to that fraction of the motoneuron pool that supplies the area of muscle underlying that specific region of skin, i.e., there is a sort of "matching" between groups of primary sensory neurons, interneurons, and motoneurons, which relates to the peripheral location of the stimulated nerve endings and of the muscle fibers that are reflexly activated. Although the partitioning of sensory input to motor nuclei has been shown most clearly for monosynaptic Ia connections, the CTM reflex suggests that sensory partitioning may also be demonstrated in a polysynaptic circuit.
Action Potentials↗
Intrinsic organization of the rat cutaneus trunci motor nucleus.
1. We have investigated how the organization of the cutaneus trunci muscle (CTM) motor nucleus might correspond to the pattern of its physiological activation (see accompanying report, 61) by using HRP to label retrogradely the motoneurons supplying different anatomically and physiologically defined muscle compartments. The CTM motoneuron pool was found to be comprised of a tightly packed column of ventrolaterally located cells extending from caudal C6 to rostral T1 and to contain 1,183 cells per side; this unusually large number of motoneurons is consistent with the precisely localized reflex behavior exhibited by the muscle. 2. Each of three major motor nerves that functionally divide the CTM into three major longitudinal muscle fields (dorsal, lateral, ventral) was found to derive from a distinct subcolumn of motoneurons, which extends for the full rostrocaudal length of the parent CTM motor nucleus, such that the dorsal motor nerves derive from a medially located subcolumn, the lateral motor nerves from a centrally located subcolumn, and the ventral motor nerves from a subcolumn of motoneurons that sits most laterally in the CTM motor nucleus. 3. Localized injections of HRP into different rostrocaudal regions of the muscle revealed a further subdivision of the CTM motor nucleus: motoneurons located rostrally in the motoneuron pool supplied the rostral regions of the muscle, whereas more caudally located motoneurons in the pool supplied progressively more caudal sites in the muscle. 4. These results reveal the existence of both a mediolateral and a rostrocaudal subdivision of the motor nucleus; thus this intrinsic spatial organization of motoneurons relates the CTM motor nucleus topographically to the body coordinates of its target, the muscle. The possible relation of these findings to the expression of local sign in the CTM reflex, and how the underlying circuitry could develop appropriately, is discussed.
Animals↗
Effects of salicylate vs. aspirin on renal prostaglandins and function in normal and sodium-depleted dogs.
The effects of aspirin (acetylsalicylate) (ASA) and nonsteroidal antiinflammatory drugs (NSAIDs) on renal prostaglandin (PG) biosynthesis and function have been studied extensively. In contrast, the in vivo effects of a nonacetylated salicylate (SA), such as sodium SA, on renal function have not been well characterized. No studies have examined the effects of SA on renal function in a situation in which the maintenance of normal kidney function is dependent upon intact renal PG synthesis (i.e., sodium restriction-elevated plasma renin activity). To evaluate the effects of SA vs ASA and/or a NSAID, normal and sodium-restricted anesthetized dogs were treated with SA and then meclofenamate (MECLO) or ASA followed by MECLO. In the normal animals, SA significantly decreased renal PGE2 and PGF2 alpha excretion. After SA a significant amount of MECLO-suppressible PGE2 and PGF2 alpha synthesis remained intact. Compared to SA, with ASA there was a greater decrease in PG excretion, with no further decrease in PG excretion with subsequent MECLO treatment. In the sodium-restricted animals (plasma renin activity, 18-24 ng of angiotensin l/ml/hr) ASA decreased PGE2 excretion but SA did not. In these animals SA did not cause renal vasoconstriction. Additional groups of sodium-restricted animals were studied with extremely high doses of ASA and SA (90 mg/kg) to elevate plasma SA to 200 to 250 micrograms/ml. In these animals SA did decrease PGE2 excretion significantly, but only to levels seen typically in normal animals and, after SA, a large amount of PGE2 excretion could be suppressed by MECLO.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗