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Biomedical subjects

J H Botting

Publications and source records attributed to J H Botting.

30 records · Page 2Linked to original sources
PubMed1975

Sensitivity of neonatal rabbit ileum to histamine.

Segments of ileum from newborn rabbits contracted in response to histamine but sensitivity declined from age 11 days. Intestine from adult animals barely contracted to histamine, even in a concentration of 3 times 10- minus 3 M. Such variation with age was not observed with acetylcholine. The response to histamine was effected by mepyramine-sensitive receptors which appeared to decrease in number as the animals aged.

Acetylcholine↗
PubMed1974

The effect of indomethacin on the release of prostaglandin E2 and acetylcholine from guinea-pig isolated ileum at rest and during field stimulation.

1 Guinea-pig ileum suspended in Krebs solution showed a continuous increase of tone which was lost by changing the bath fluid. Prostaglandin E(2) was released from the ileum during incubation, and its concentration in the bath fluid appeared to correlate with the increase in tone.2 Supramaximal field stimulation (10 Hz) resulted in increased release of prostaglandin E(2) from the ileum. At lower rates of stimulation, the increase in the release of E(2) compared with the resting output was not significant.3 Indomethacin (1 and 10 mug/ml) produced a significant, dose-related reduction of the amount of prostaglandin E(2) measured in the bath fluid at rest and with field stimulation. Indomethacin inhibited the contraction of the ileum during incubation in Krebs solution.4 Indomethacin (10 and 20 mug/ml) had no significant effect on the release of acetylcholine during field stimulation, but reduced the resting output of acetylcholine from guinea-pig ileum in some experiments.5 The results are discussed in the context of the role ascribed to prostaglandins as physiological modulators in transmitter release. No evidence for a prostaglandin-mediated negative feedback mechanism on acetylcholine release was obtained.

Acetylcholine↗
PubMed1969

Studies on the mode of action of vasopressin on the isolated proximal colon of the guinea-pig.

1. Contractions of guinea-pig isolated proximal colon produced by vasopressin are not affected by methyloxytocin (a compound that blocks pressor effects of vasopressin).2. Vasopressin contractions are inhibited by replacement of sodium with mannitol or sucrose, elevation of potassium or magnesium concentrations, the presence of the metabolic inhibitors sodium azide and triethyl tin or tetrodotoxin in the bathing fluid. Contractions produced by histamine or choline esters are comparatively insensitive to these procedures.3. Contractions of rat isolated uterus following vasopressin, oxytocin and methacholine are equally affected by replacement of sodium, increase of potassium or magnesium or addition of sodium azide.4. Neither vasopressin contractions nor contractions caused by transmural stimulation were consistently affected by morphine (10(-6) g/ml.) or hyoscine (10(-7) g/ml.) although both were reduced by anoxia or cooling the tissue. Morphine did not reduce the output of acetylcholine from stimulated colon.5. It is concluded that the action of vasopressin on proximal colon is unlike its action on other smooth muscle and is mediated by nervous tissue.

Acetylcholine↗
PubMedDate not supplied

Nonsteroidal antiinflammatory agents.

Since the synthesis of aspirin in 1897, aspirin-like or nonsteroidal antiinflammatory drugs (NSAIDs) have been the mainstay of therapy for rheumatoid arthritis. Although of diverse chemical structure, these drugs not only exhibit the same antipyretic, analgesic and antiinflammatory therapeutic actions, but they also manifest identical toxic actions on the gastric mucosa and the kidney. This indicated that a single pharmacological effect was responsible for the properties of NSAIDs, a theory that was confirmed by the epochal discovery by Vane in 1971, that inhibition of the enzyme-producing prostanoids (cyclooxygenase [COX]) produced both the therapeutic and side effects of aspirin-like drugs. However, at equivalent antiinflammatory doses, different NSAIDs exhibited different degrees of toxicity. The reason for this was resolved by the discovery that prostaglandins at sites of tissue damage were synthesized by an inducible COX (COX-2) formed by a gene distinct from that producing the constitutive enzyme (COX-1), responsible for the formation of prostaglandins that serve an essential physiological function. Modification of the structure of drugs showing a moderately selective effect on COX-2, and the elucidation of the crystal structure of both enzymes, has paved the way for the synthesis of NSAIDs that are highly selective for the inducible enzyme and which are, therefore, antiinflammatory without the typical side effects of the classical NSAIDs. The focus on COX-2 has also expanded our knowledge of the pathophysiological significance of prostanoids and raised the possibility of new uses for selective COX-2 inhibitors, for example, in colon cancer, premature labor and possibly Alzheimer's disease. However, the clinical effects of chronic administration of potent, selective COX-2 inhibitors must await the results of ongoing clinical trials.

Journal Article↗
PubMedDate not supplied

Relationship between gender difference in intravascular aggregation of platelets and the fibrinolytic pathway in the rat.

Intravascular aggregation of platelets was evaluated in relation to the fibrinolytic system in order to assess the possibility of a "cause-effect" relationship. The spontaneous fibrinolytic activities of the plasma of male rats and of female rats at the various stages of the oestrous cycle were determined. Male rats had higher euglobulin clot lysis time (54.5 +/- 5.3 vs 29.2 +/- 3.1 min; P less than 0.05), higher fibrinogen levels (330.0 +/- 15.8 vs 231.0 +/- 31.1 mg/dl; P less than 0.025) and higher plasminogen activity (8.1 +/- 1.2 vs 6.1 +/- 1.6 plasmin units/ml; P less than 0.05) than female rats. Female rats had higher fibrinolytic index (8.8 +/- 0.8 vs 6.3 +/- 0.3 mg/dl; P less than 0.05) and plasminogen activator activity (99.1 +/- 6.0 vs 76.5 +/- 7.7 Plough units/ml; P less than 0.05) than male rats. The antiplasmin activities were the same in both sexes. During the oestrous cycle in female rats, euglobulin clot lysis time was not significantly different though it was highest during met-oestrous (34.2 +/- 3.6 min). However, pro-oestrous rats had lower fibrinogen (122.9 +/- 5.3 mg/dl; P less than 0.005), higher fibrinolytic index (10.6 +/- 0.8 mg/dl/min; P less than 0.001) and higher plasminogen activator activity (109.4 +/- 7.8 Plough units/ml; P less than 0.05) than rats from the other stages of the oestrous cycle. There were no significant differences in plasminogen content and antiplasmin activity. Using native rats, aggregatory responses to submaximal doses of adenosine diphosphate (20 micrograms/kg) were determined and correlated with the fibrinolytic data in age- and weight-matched rats (of both sexes). Aggregatory responses in all the groups of rats used correlated positively with fibrinogen levels (r = 0.8316; P less than 0.001) and negatively with plasminogen activator activity (r = -0.7839; P less than 0.05). Streptokinase (250-1000 Plough units/kg/hr) and urokinase (1000-4000 Plough units/kg/hr) produced dose-related reductions in intravascular aggregation induced by adenosine diphosphate. The streptokinase effect (but not urokinase effect) was reversed by epsilon-aminocaproic acid. Following the cessation of infusion of streptokinase and urokinase, there was a recovery of the platelets to aggregate to adenosine diphosphate. These observations suggest fibrinolytic pathway-specific effects. However, on its own, epsilon-amino-caproic acid did not affect the aggregatory responses of platelets from pro-oestrous rats. These results suggest that changes in fibrinolytic mechanisms may account for differences observed in intravascular aggregation of platelets of male and female rats and of female rats during the oestrous cycle.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMedDate not supplied

Pharmacodynamic interaction between oestradiol and adrenaline on intravascular aggregation induced by adenosine diphosphate in the rat.

Physiological levels of oestradiol and adrenaline inhibit intravascular aggregation of platelets, and effect dependent on the presence of an adrenal gland secretion (possibly adrenaline) and oestrogens, respectively. This infers a "mutual dependence" phenomenon. Acute adrenalectomy had a biphasic effect on intravascular aggregation: enhancing platelet aggregation when levels of oestradiol are high, e.g. in pro-oestrous rat, and reducing platelet aggregation when levels of oestradiol are nil or very low, i.e., in ovariectomized or di-oestrous rats, respectively. Ovariectomy also had a biphasic effect on platelet aggregation reducing aggregation in the absence of adrenaline and enhancing aggregation in its presence. Removal of endogenous oestradiol (by ovariectomy) and its replacement fully corroborates the "mutual dependence" hypothesis, whereas the removal of endogenous adrenaline (by acute adrenalectomy) and its replacement only partially supports it. It is concluded that, though both oestradiol and adrenaline have inhibitory effects on intravascular aggregation at physiological doses, each seems to need the full compliment of the other to achieve the effect.

Adenosine Diphosphate↗
PubMedDate not supplied

Inhibition of intravascular platelet aggregation in the rat by adrenaline.

Intravascular platelet aggregation to adenosine diphosphate (ADP) was measured in anesthetized rats using 111indium-labelled platelets. Acute adrenalectomy increased the aggregatory effect of ADP in vivo, whereas infusions of low concentrations of adrenaline into adrenalectomized rats suppressed ADP-induced platelet aggregation. Similar antiaggregatory effects were seen with the alpha 2 agonist B-HT 933 and the alpha 1 agonist methoxamine, but not with isoprenaline. The effect of adrenaline was inhibited by phentolamine, yohimbine, the selective alpha 2 adrenoceptor antagonist WY 26392 and by indomethacin, but not by propranolol or prazosin. Adrenaline thus inhibits ADP-induced aggregation in vivo by a mechanism that may involve stimulation of an alpha 2 adrenoreceptor and may be dependent on activation of cyclooxygenase enzyme.

Adenosine Diphosphate↗