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Biomedical subjects

E S Johnson

Publications and source records attributed to E S Johnson.

At least 145 records · Page 8Linked to original sources

Ovulation and gonadotropin-releasing activity of [p-LEU-6, DES-GLY NH2-10, pro-ethylamide-9] -GNRH.

The ovulation-inducing and gonadotropin-releasing activities of [d-Leu-6, des-Gly NH2-10, Pro-ethylamide-9]-GnRH (II), were evaluated in rats, rabbits, and sheep. A sc dose of 3.4 ng/100 g body wt of the analog was equal to 160 ng/100 g body wt of GnRH in causing ovulation in the diestrous rat. At these dose levels, the integrated LH release was 1.9 times greater for the analog. Both the time of increase and maximum serum concentrations of LH were delayed after injection of the analog. Oral administration of II and GnRH to the proestrous rat resulted in an ED50 for ovulation of 0.92 and 54 mug/100 g body wt,respectively. Serum levels of LH and FSH were highly variable for the various treatment groups when both releasing substances were administered orally. The intense ovulating activity of II was also evident in the estrous rabbit as indicated by an activity 31 times greater than that of GnRH. Additionally, the analog was at least 50 times more active than GnRH in releasing LH in both the mid-luteal and anestrous ewe. From our experiments with the cycling rat it appears that the intense ovulation-inducing activity of II can be accounted for by the intrinsic LH-releasing activity of the nonapeptide, rather than by a prolonged release stimulus.

Administration, Oral↗

Quantitative analysis on isolated organs of the autonomic blocking properties of indoramin hydrochloride (Wy 21901).

1. Indoramin is a competitive alpha-adrenoceptor blocking agent on the guinea-pig isolated vas deferens and aortic strip; the pA(2) value on the aorta is 7.4.2. Indoramin is devoid of beta-adrenoceptor blocking activity on the guinea-pig isolated trachea (10(-4)M) and the Langendorff preparation of the rabbit heart (10(-6)M). It also has no adrenergic neurone blocking action on the Finkleman preparation of the rabbit small intestine (10(-5)M).3. On the Langendorff preparation of the rabbit isolated heart, indoramin (above 10(-6)M) has cardio-inhibitory properties similar to those of propranolol.4. On the guinea-pig isolated ileum (10(-5)M) and trachea (10(-6)M), indoramin is devoid of anticholinergic activity, but has a potent antihistamine action which satisfies the criteria for competitive antagonism; the pA(2) value for this antagonism on the ileum is 8.2.5. Indoramin antagonizes 5-hydroxytryptamine on the rat isolated fundus and ileum; the pA(2) value for the antagonism on the ileum is 6.0.

Adrenergic alpha-Antagonists↗

Amino-acid induced depression of cortical neurones.

1. The effects of strychnine on the degree of depression of neuronal firing induced by glycine, gamma-aminobutyric acid (GABA) and 5-hydroxytryptamine (5-HT) have been examined quantitatively. All drugs were applied by iontophoresis to spontaneously active cerebral cortical neurones in the anaesthetized cat. The application of these drugs was continued until a plateau or equilibrium depression was reached. The time taken to reach this steady state was noted. Dose-response curves were then constructed for those currents giving less than complete depression.2. Glycine was less potent than GABA and about 7-fold larger currents were needed to achieve comparable depression. 5-HT was also a weak depressant compared with GABA and had 0.6 the potency of glycine on a current basis.3. Strychnine in currents up to 25 nA shifted the dose-response curve of glycine to the right at a time when equilibrium depression in the same cells induced by the control agonists GABA or 5-HT was unaffected. These currents of strychnine did, however, prolong the time-course of onset of GABA and 5-HT depression.4. In larger currents strychnine reduced GABA equilibrium depression, but the dose-response curve was not shifted in a parallel fashion.5. It is concluded that strychnine can specifically and competitively antagonize the effect of glycine on cortical neurones.

Action Potentials↗