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Biomedical subjects

M Brann

Publications and source records attributed to M Brann.

9 recordsLinked to original sources
PubMed2001

Exploring the potential for subtype-selective muscarinic agonists in glaucoma.

Pilocarpine has been used to lower intraocular pressure (IOP) in glaucoma patients for more than 100 years. Since the identification of five muscarinic receptor subtypes, there has been an interest in separating the IOP-lowering effects from the ocular side effects of pupil constriction and lens accommodation. However, all these actions seem to be mediated by the M3 receptor. A novel muscarinic receptor agonist, AGN 199170, that has no activity on the M3 subtype was compared to pilocarpine in a monkey glaucoma model. This compound lowered IOP suggesting that muscarinic agonists targeted at muscarinic receptors other than the M3 subtype may be able to selectively lower IOP.

Animals↗
PubMed1996

A serotonin receptor gene (5HT1A) variant found in a Tourette's syndrome patient.

Serotonergic pathway disturbances have been implicated in neuropsychiatric disorders such as Tourette's syndrome (TS), substance abuse, and depression. In order to search for the presence of an association between these neuropsychiatric disorders and particular serotonin receptors isolated from these patients, we have started to analyze the structure of these receptor genes. We now report that a missense nucleotide change in the 5HT1A receptor gene produces a variant form of the 5HT1A receptor (Arg(219) to Leu) identified in DNA extracted from a TS patient. Also, in several DNA samples examined, both in controls and in the patients, we found a second missense nucleotide change which resulted in an amino acid change (Asn(417) to Lys) located in the carboxyl tail of the receptor. Several other polymorphic changes have been reported previously in the human 5HT1A receptor and we have also confirmed these findings in our samples.

Alcoholism↗
PubMed1995

In vitro and in vivo evaluation of the subtype-selective muscarinic agonist PD 151832.

PD 151832 is a potent partial muscarinic agonist that displays a high level of functional selectivity for the muscarinic m1 receptor subtype, as evidenced by its selective stimulation of PI turnover and cellular metabolic activity in transfected Hm1-CHO cells at concentrations that produce minimal stimulation of other cloned human muscarinic receptors. PD 151832 enhanced the amplification of Hm1-transfected NIH-3T3 cells at concentrations lower than those required to produce similar effects in Hm2 or Hm3-transfected cells. The functional m1 selectivity of PD 151832 is consistent with its improvement of mouse water maze performance at doses far lower than those required to produce peripheral parasympathetic side effects.

3T3 Cells↗
PubMed1987

Detection of multiple forms of Gi alpha in HL60 cells.

Comparison of cDNA sequences from multiple sources predicts a genus of highly homologous but structurally distinct G protein alpha-subunits, designated as Gi alpha, that may include the alpha-subunit of the functionally defined adenylate cyclase inhibitory G protein. Using specific oligonucleotide probes on Northern blots, we show that Gi alpha-2 and Gi alpha-3, but not Gi alpha-1, are expressed in HL60 cells. Antisera raised against synthetic peptides from regions predicted to be conserved (AS6) and divergent (LE3) among Gi alpha subtypes bind to a 40 kDa protein in Western blots of HL60 membranes. AS6 identifies an additional protein at 41 kDa. Thus, Northern blot and immunoblot results show that at least two Gi alpha subtypes, a 40 kDa protein likely to correspond to Gi alpha-2 and a 41 kDa protein possibly representing Gi alpha-3, may be expressed in a single cell type.

Amino Acid Sequence↗
PubMed1985

The use of [3H](-)-DO 710 as selective dopaminergic ligand for binding and autoradiographic studies.

DO 710, a benzamide derivative previously shown to display a dopamine antagonistic potency superior to that of sulpiride, was 3H-labeled. Its use as radioligand was assessed in membrane binding and autoradiographic studies. The compound displayed relatively high affinity (Kd 2 nM) and pronounced selectivity for dopamine receptors (distinct from D-1 receptors) as well as low non-specific binding particularly evidenced in autoradiographic experiments. Hence [3H](-)-DO 710 displays distinct technical advantages over commonly used dopaminergic radioligands.

Animals↗
PubMed1985

3H-(-)DO 710 discriminates guanine nucleotide sensitive and insensitive dopamine binding sites.

(-)DO 710, a substituted benzamide derivative which discriminates dopamine D-2 and D-4 binding sites (Sokoloff et al. 1984), and antagonises in a differential manner several apomorphine-induced behavioral responses (Schwartz et al. 1984) was tritiated and used namely to differentially label the D-4 site. In striatum the 3H-(-)DO 710 saturation curve was best explained by the presence of two classes of sites with a 7-fold difference in affinity (Kd values of 3.0 nM and 0.42 nM) and Bmax values of 316 and 106 fmol X mg protein-1, respectively which correspond to the D-2 and D-4 sites (Sokoloff et al. 1984). In spite of its limited selectivity, 3H-(-)DO 710 in low concentration (0.2 nM) could be used to preferentially label striatal D-4 site as shown by the inhibition potencies of discriminant benzamide derivatives (DBD), significantly higher than at pituitary D-2 site (receptor) whereas classical neuroleptics including metoclopramide were equally potent at both sites. The affinity of a variety of agonists for striatal sites labeled with 0.2 nM 3H-(-)DO 710 generally differed from their affinity for the two states of the pituitary D-2 receptor (with high and low affinity for agonists, respectively); compounds like lisuride, N-propylnorapomorphine or pergolide had very high affinity for the striatal 3H-(-)DO 710 site. In pituitary from oestradiol-treated rats, where only D-2 site occurs, only the low-affinity site for 3H-(-)DO 710 (Kd = 2.8 nM) was found.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1971

Illogical truths.

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