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Biomedical subjects

A Pfeiffer

Publications and source records attributed to A Pfeiffer.

At least 145 records · Page 8Linked to original sources
PubMed1989

Evaluation of the gastric absorption and emptying of drugs under various pH conditions using a simple intubation method: application to diclofenac.

Sodium diclofenac (50 mg) together with [14 C]-PEG as a non-absorbable marker were dissolved in 400 ml of water (A), phosphate buffer pH 7.5 (B) or a homogenized meal (C). Each of these was ingested in random order by six volunteers on 3 consecutive days. Some gastric absorption of the drug was established with C but the plasma drug concentration-time profiles mainly reflected the process of gastric emptying.

Absorption↗
PubMed1989

Effect of jejunal infusion of nutrients on gastrointestinal transit and hormonal response in man.

The effects of jejunal infusion of nutrients on gastric emptying and secretion, intestinal transit and hormone release were studied in human volunteers. Two caloric loads, 1.3 and 3.3 kcal/min, of a nutrient solution consisting of 18 percent protein, 27 percent lipids, and 55 percent carbohydrates were tested. These were first used in random order in 6 subjects to assess the effects on intestinal transit. For the study of gastric emptying, jejunal infusion was started 1 h after intragastric instillation of a 490 kcal, 400 ml, homogenized meal. Intestinal transit time and gastric emptying half-time increased with the rate of nutrient infusion into the jejunum. Postprandial gastric secretion was reduced. The two caloric loads induced significant rises of plasma cholecystokinin and gastric inhibitory polypeptide concentrations. Plasma motilin decreased in relation to the jejunal caloric load. The other peptides were essentially not affected by jejunal nutrient infusion in fasting subjects. We conclude that in man, gastric emptying rate, gastric secretion, and intestinal transit are regulated by the presence of nutrients in the jejunum.

Adult↗
PubMed1988

Different binding properties of muscarinic M2-receptor subtypes for agonists and antagonists in porcine gastric smooth muscle and mucosa.

The hypothesis that muscarinic receptors on smooth muscle differ from those in epithelial glands was tested by comparing the properties of muscarinic binding sites in porcine fundic smooth muscle with those in mucosal membranes. The binding of agonists and of antagonists was assessed by displacement of [3H]N-methylscopolamine. Pirenzepine (M1-antagonist) labeled low-affinity binding sites in smooth muscle (KD = 229 nM) and in mucosa (KD = 124 nM) consistent with the presence of M2 sites. Carbachol interacted with a high-affinity (KD = 164 nM) and a low-affinity (KD = 18.2 microM) state of binding sites in smooth muscle. Guanyl 5'-yl-imidodiphosphate converted all sites to the low-affinity state. N-ethylmaleimide pretreatment increased the affinity of carbachol and the proportion of high-affinity sites. In clear contrast, only low-affinity sites of carbachol were detectable in mucosa (KD = 17 microM) that were not modulated by N-ethylmaleimide or guanyl 5'-yl-imidodiphosphate. The cardioselective antagonist AF-DX 116 displayed low affinity to mucosal binding sites (KD = 3.4 microM), whereas its affinity to smooth muscle was 503 nM. The antagonist hexahydro-sila-difenidol had a very high affinity (KD = 2.9 nM) to mucosal receptors, whereas its affinity to smooth muscle sites was 88 nM. These data show that muscarinic M2 binding sites in mucosa and smooth muscle can be distinguished by both agonist and antagonist binding experiments, and suggest the existence of different subtypes of M2-binding sites in these tissues.

Animals↗
PubMed1988

Glucocorticoid receptor gene expression in rat pituitary gland intermediate lobe following ovariectomy.

Using hybridization techniques and Northern blots we have identified a approximately 6.5 kb glucocorticoid receptor mRNA species in rat pituitary intermediate lobe. Glucocorticoid receptor mRNA concentrations, which are barely detectable or undetectable in normal animals, were greatly increased following ovariectomy. This ovariectomy-induced increase in glucocorticoid receptor mRNA content of the intermediate lobe, which was confirmed by in situ hybridization experiments, could be reversed by 17 beta-estradiol administration.

Animals↗
PubMed1988

Effect of different caloric loads in human jejunum on meal-stimulated and nonstimulated biliopancreatic secretion.

The effects on biliopancreatic secretion of two caloric loads (1.3 and 3.3 kcal/min of Realmentyl: proteins 18%, lipids 27%, carbohydrates 55%), infused into the jejuna of 10 healthy men, were compared with those of a control solution. In one set of experiments (six subjects) when biliopancreatic secretion was not stimulated before infusion, the rate 1.3 kcal/min resulted in mild stimulation whereas the rate 3.3 kcal/min brought about an inhibition of biliopancreatic secretion. In another set of experiments (six subjects) when biliopancreatic secretion was stimulated by ingestion of an homogenized meal (400 mL, 490 kcal) 1 h before the start of infusion, both loads resulted in strong inhibition of pancreatic secretions, the effect being more pronounced with the high caloric load.

Adult↗
PubMed1988

Stimulation of acid secretion and phosphoinositol production by rat parietal cell muscarinic M2 receptors.

The muscarinic receptor system involved in hydrogen ion production by enriched rat gastric parietal cells was investigated. Muscarinic receptor density determined by [N-methyl-3H]scopolamine binding was 8,100/cell. The receptor appeared to be of the M2 muscarinic receptor subtype, since it had a low affinity (Kd, 189 nM) for the M1 receptor antagonist pirenzepine compared with atropine (Kd, 0.74 nM). Receptor activation by carbachol rapidly augmented levels of polyphosphoinositides, indicating an activation of a phospholipase C. The dose-response relations for the increase in inositol phosphates closely paralleled the binding of carbachol to muscarinic receptors with a Km of 17 microM. The inositol phosphate response was antagonized by pirenzepine with a Ki of 177 nM. The stimulation of inositol phosphate levels by carbachol correlated well with the stimulation of [14C]aminopyrine uptake, determined as an index of acid secretion. The muscarinic agonists oxotremorine, pilocarpine, and bethanechol elicited partial increases in inositol phosphates at maximal drug concentrations, and these partial increases correlated with their ability to stimulate [14C]aminopyrine uptake. These data indicate that inositol polyphosphates may be a second messenger of M2 receptors stimulating acid secretion.

Aminopyrine↗
PubMed1987

Transfer of functional opiate receptors from membranes to recipient cells by polyethylene glycol-induced fusion.

Opiate receptor-mediated inhibition of adenylate cyclase activity was elicited in membranes of C6BUI glioma cells and S49 cyc- lymphoma cells after fusion with opiate receptor-containing membranes derived from NG108-15 neuroblastoma x glioma hybrid cells. The fusion was induced by polyethylene glycol using procedures developed by Orly and Schramm [(1976) Proc. Natl. Acad. Sci. USA 73, 4410-4414]. Prior to fusion, the adenylate cyclase activity of the donor. NG108-15 cell membrane, was inactivated by N-ethylmaleimide treatment. Prostaglandin E1 receptors and the stimulatory GTP-binding protein Ns were transferred to the recipient cells along with opiate receptors. Thus, inhibitory receptors can be transferred to foreign adenylate cyclase systems just as stimulatory receptors had earlier been found to do. Furthermore, opiate receptors have been shown to function in non-neuronal cells.

Adenylyl Cyclase Inhibitors↗
PubMed1987

delta EPhe4-enkephalin analogs. Delta receptors in rat brain are different from those in mouse vas deferens.

Conformationally restricted enkephalin analogs containing E-cyclopropylphenylalanine (delta EPhe), [D-Ala2, (2R,3S)-delta EPhe4,Leu5]enkephalin and its (2S,3R) isomer, were evaluated in receptor-binding assays using rat brain and in assays using muscle preparations. The (2S,3R) isomer was almost completely inactive in all assays. In contrast, the (2R,3S) isomer showed a very high affinity for the delta and a very weak affinity for the mu receptors in rat brain. The extent of delta affinity and the selectivity of this isomer were almost equal to those of [D-Pen2,D-Pen5]enkephalin. However, the (2R,3S) isomer was inactive in both the mouse vas deferens and guinea pig ileum assays, and showed no antagonistic activity in these tissues. These results indicate that the (2R,3S) isomer interacts with the delta receptors in rat brain, but not with those in the mouse vas deferens, and they suggest that the delta receptors in the central and peripheral nervous systems are different from each other.

Animals↗
PubMed1987

The role of CRF in the release of ACTH by opiate agonists and antagonists in rats.

Opiate agonists as well as opiate antagonists release adrenocorticotropic hormone (ACTH) through unknown central mechanisms. We examined the role of corticotropin releasing factor (CRF) in opioid actions on ACTH release. Rats were pretreated with a specific antiserum to rat CRF (r-CRF) prior to injection of the opiate antagonist naloxone or the opiate agonists morphine (mu-receptor agonist) or MR 2034 (kappa-receptor agonist). This abolished the increase in ACTH caused by naloxone or by the kappa-agonist. The mu-agonist morphine, however, caused a significant increase in ACTH in control- or r-CRF antiserum treated rats. We conclude that (a) endogenous opioids tonically inhibit the release of CRF, (b) kappa-agonists stimulate the release of CRF, and (c) mu-agonists release ACTH by acting additionally through CRF-independent mechanisms.

Adrenocorticotropic Hormone↗
PubMed1987

Functional and biochemical interaction of dibutyryl cyclic AMP with the phosphoinositide system in isolated rat parietal cells.

The interaction of the muscarinic agonist carbachol and of dibutyryl cAMP on acid secretion and phosphoinositide second messenger metabolism were studied in rat gastric parietal cells. Compared to the added effects of each agonist alone aminopyrine uptake, a measure of acid secretion, was enhanced 2-4-fold by the combination of both compounds. In addition the ED50 for carbachol was left shifted in the presence of dibutyryl-cAMP. The cholinergic stimulation of inositol phosphate production was slightly inhibited by dibutyryl-cAMP while levels of diacylglycerol were not affected. Thus the interaction of the cAMP and the phosphoinositide systems involve potentiation and positive sensitivity modulation of the cholinergic response by cAMP which is mediated by events distal to the generation of phosphoinositide second messengers.

Aminopyrine↗
PubMed1987

[Recurrent menstruation-associated pneumothorax--catamenial pneumothorax].

The case of a 28-year old patient with a rare complication of an extensive endometriosis externa is described. A spontaneous pneumothorax occurred on 3 occasions corresponding each time with the start of the menstrual period. The various hypotheses on the aetiology and treatment of this rare condition are reviewed. To date only 65 patients with this interesting clinical entity have been recorded.

Adult↗
PubMed1987

Jejunal and ileal absorption of oxprenolol in man: influence of nutrients and digestive secretions on jejunal absorption and systemic availability.

1 Study I evaluated the absorption of oxprenolol in the ileum, compared to jejunum, in healthy volunteers by an intestinal perfusion technique. Around 80 mg of drug were delivered as a saline solution directly in the small bowel. 2 Samples taken 30 cm distally to the site of perfusion showed that 63% of perfused oxprenolol was absorbed in the jejunum and 48% in the ileum; the differences were significant. 3 The plasma concentration-time profiles were similar for the two perfusions. The AUC and Cmax values of free and conjugated oxprenolol for the jejunal perfusion were significantly lower than those of ileum. They showed large but consistent intersubject variations in the two treatments. 4 Study II investigated, using the same technique, the influence of nutrients and digestive secretions on jejunal absorption and systemic availability of this drug. A saline (in treatments A and B) or a nutrient (in treatment C) solution containing oxprenolol was perfused into the jejunum below a balloon either inflated (A) or deflated (B and C). 5 The disappearance rate of oxprenolol from the jejunum was unaffected by endogenous secretions. The mean amount of drug absorbed along a 30-cm jejunal segment accounted for 52 (A) and 57% (B) of the total amount perfused. The intestinal absorption rate was markedly increased in the presence of nutrients (mean amount absorbed 96% for C). 6 The change in the rate of disappearance from the intestine had no effect on the systemic availability of oxprenolol (mean AUC values 8740, 8250 and 8020 nmol l-1 h for A, B and C, respectively) or its elimination from plasma.(ABSTRACT TRUNCATED AT 250 WORDS)

Biological Availability↗
PubMed1987

Opiate suppression of LH secretion involves central receptors different from those mediating opiate effects on prolactin secretion.

The involvement of mu- and kappa-opiate receptors in the regulation of LH and prolactin secretion was investigated in long-term ovariectomized rats using selective opiate receptor agonists and antagonists. The mu-agonists morphine and [D-Ala2,MePhe4,Gly5-ol]-enkephalin (DAGO) suppressed LH levels in a dose-related manner. The benzomorphane (-)-5,9-dimethyl-2'-hydroxy-2-(tetrahydrofurfuryl)-6,7-benzomorphan tartrate (MR 2034; a designated kappa-agonist) also suppressed LH levels, whereas another benzomorphane kappa-agonist (-)-5,9-dimethyl-2'-hydroxy-2-(2-methoxy-propyl)-6,7-benzomorphan hydrobromide (MRZ 2549) had no effect on the levels of this hormone. Pretreatment with the highly selective mu-antagonist beta-funaltrexamine (beta-FNA), the fumarate methyl ester derivative of naltrexone, blocked the actions of both mu-agonists and MR 2034, indicating that opiate suppression of LH secretion is mediated by mu-receptors. This was further confirmed by in-vitro studies: the KCl-induced release of LHRH from perifused hypothalami obtained from ovariectomized rats was significantly reduced by DAGO but not by MRZ 2549. Prolactin secretion was stimulated in a dose-dependent manner by both mu- and kappa-agonists. The stimulation caused by morphine and DAGO was antagonized by beta-FNA, whereas that caused by the kappa-agonists MR 2034 and MZR 2549 was resistant to blockade by beta-FNA but not by naloxone (an antagonist which blocks all classes of opiate receptors when given in high doses). Thus prolactin secretion seems to be regulated by both mu- and kappa-opiate receptors, whereas the effects on LH secretion seem to involve mu-receptors only.

Animals↗
PubMed1986

Muscarinic M2-receptors enhance polyphosphoinositol release in rat gastric mucosal cells.

Muscarinic receptor types and their effects on the inositol phosphate second messenger system were studied in enzymatically dispersed rat gastric mucosal cells. Radioreceptor binding studies indicated the presence of a single class of binding sites (4860 +/- 875 sites/cell) and affinities of 0.42 +/- 0.12 nM, 176 +/- 32 nM and 13 microM for N-methylscopolamine, pirenzepine and carbachol, respectively. In cells prelabelled with myo-[3H]inositol carbachol induced a dose-dependent increase in inositol-1-phosphate in the presence of lithium with an ED50 of 10 microM which was antagonized by atropine and pirenzepine (IC50 9 and 700 nM, respectively). Carbachol stimulated amino[14C]pyrine uptake, used as a measure of acid secretion, with an ED50 of 10 microM. The good correlation between these responses suggests a role for inositol phosphates in the muscarinic M2-receptor mediated acid secretion.

Aminopyrine↗
PubMed1986

Psychotomimesis mediated by kappa opiate receptors.

The kappa opioid agonists are analgesics that seem to be free of undesired morphine-like effects. Their dysphoric actions observed with the kappa agonist cyclazocine are thought to be mediated by an action at sigma-phencyclidine receptors. The benzomorphan kappa agonist MR 2033 is inactive at sigma-phencyclidine receptors. In male subjects, the opiate-active (-)-isomer, but not the (+)-isomer, elicited dose-dependent dysphoric and psychotomimetic effects that were antagonized by naloxone. Thus, kappa opiate receptors seem to mediate psychotomimetic effects. In view of the euphorigenic properties of mu agonists, our results imply the existence of opposed opioid systems affecting emotional and perceptual experiences.

Adult↗