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Biomedical subjects

J Brownell

Publications and source records attributed to J Brownell.

42 records · Page 3Linked to original sources
PubMed1980

Inhibitory action of a met-enkephalin on ACTH release in man.

In order to study the mechanism of action of a Met-enkephalin (FK 33824) on the pituitary-adrenal axis eight normal male volunteers were subjected to an ACTH stimulation test. Lysine-vasopressing (LVP), 5 IU, was injected intramuscularly after pretreatment with 0.5 mg FK 33824 i.m. or a placebo. In six of the subjects the opiate was again administered preceding a single injection of 0.25 mg ACTH beta 1-24 i.m. Blood was collected at regular intervals and ACTH and cortisol concentrations analyzed in all samples. LVP induced significant plasma ACTH (P < 0.05) and cortisol (P < 0.001) increases. Pretreatment with FK 33824 completely antagonized the effect of LVP. Furthermore, the cortisol elevation after exogenous ACTH was not modified by previous administration of FK 33824. It is concluded that the Met-enkephalin derivative FK 33824 directly suppresses ACTH release from the pituitary without influencing adrenal synthesis of cortisol.

Adrenal Glands↗
PubMed1980

Inhibition of vasopressin secretion by a met-enkephalin (FK 33-824) in humans.

To investigate the effect of a met-enkephalin analogue, FK 33-824, on renal handling of water, 8 subjects were given 0.5 mg im of the drug or placebo in a cross-over study. In a second trial under the same testing conditions, a 4 mg dose of naloxone iv was given to 6 subjects immediately preceding 0.5 mg FK 33-824 im. Urine and blood samples were collected at hourly intervals. Urinary vasopressin (AVP) and plasma prolactin (Prl) were assayed, and free water clearance (FWC) was calculated. Following the same protocol, a further 6 subjects received 5 IU of lysine vasopressin im 5 min preceding administration of FK 33-824. FK 33-824 significantly (P < 0.001) increased Prl and FWC and reduced urinary concentrations of AVP (P < 0.01). Naloxone pre-treatment failed to modify significantly the latter two responses, while Prl stimulation was inhibited. Lysine vasopressin pre-treatment abolished the effect of FK 33-824 on FWC while the stimulating action on Prl was preserved. These results indicate that in humans FK 33-824 reduces AVP secretion and that this effect is not mediated by naloxone sensitive opiate receptors.

Adult↗
PubMed1979

Poly(2-fluoroadenylic acid). The role of basicity in the stabilization of complementary helices.

The polymerization of 2-fluoroadenosine 5'-diphosphate by polynucleotide phosphorylase to give high molecular weight poly(2-fluoroadenylic acid), poly(fl2A), is described. Both the single-stranded and double-stranded (acid) forms of poly(fl2A) exhibit strikingly similar ultraviolet and circular dichroism spectra to those of poly(A), and the enzymatic polymerization rates and thermal hyperchromicities of the two polymers are also very similar. However, the pKa of poly(fl2A) for protonation at N-1 is 2.9 compared to 5.9 for poly(A) under similar conditions. Poly(fl2A) forms a triple-stranded helix with poly(U) which has ultraviolet and cd spectra very reminiscent of poly(A) . 2 poly(U), but no conditions could be found which permitted the formation of a double helix. In the Escherichia coli ribosome system poly(fl2A) codes for the synthesis of polylysine, as does poly(A), although the rate and extent of incorporation were less in the former case. The role of basicity of adenine N-1 in these interactions is discussed.

Drug Stability↗
PubMed1979

Prolactin. I. Mechanisms of control, peripheral actions and modification by drugs.

The role of neurotransmitters in the release of prolactin (PRL) is reviewed. Special attention is paid to dopamine (DA) as the possible prolactin-inhibiting factor (PIF). Among other agents, estrogens alone can act directly on the pituitary galactotropes without involving hypothalamic factors. Peripherally, in addition to its stimulatory action on mammary tissue, PRL exerts a permissive role on ovarian steroidogenesis. A possible physiological action of this hormone on the regulation of adrenal function remains uncertain. The secretory rhythms of PRL are described and the mechanisms involved are discussed. A number of drugs can modify the secreting pattern of PRL mainly by acting on the dopaminergic control mechanisms. The usefulness of such agents in the clinical evaluation of galactotrope cell function is reviewed.

Adolescent↗
PubMed1978

Photoaffinity labeling of the ribosomal peptidyl transferase site with synthetic puromycin analogues.

A photoaffinity labeling puromycin analogue, Nepsilon-(2-nitro-4-azidophenyl)-L-lysinyl puromycin aminonucleoside (NAP-Lys-Pan), was synthesized and used for investigation of the peptidyl transferase center of 70S riobsomes. Visible light irradiation of NAP-Lys-Pan led to covalent linkage of the analogue with Escherichia coli ribosomes. In a subsequent step, poly(uridylic acid) was employed to direct Ac[14C]Phe-tRNA to the P sites of the photolabeled ribosomes. Transpeptidation of Ac[14C]phenylalanine to the bound NAP-Lys-Pan resulted in selective incorporation of radioactive label into the peptidyl transferase A site. Dissociation of the ribosomes into subunits, and digestion of the RNA components, indicated that the radioactive label was incorporated into a protein fraction of the 50S subunit.

Acyltransferases↗