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Biomedical subjects

B Donoff

Publications and source records attributed to B Donoff.

10 recordsLinked to original sources
PubMed1991

Functional subtyping of muscarinic receptors on canine esophageal mucosa.

Serosal addition of muscarinic agonists elicited rapid changes in electrical parameters across the isolated canine esophageal epithelium set up in vitro. Both carbachol and the M1-selective agonist, McNeil A343 (McN), increased transmucosal potential differences (PDs), decreased transmucosal resistances (R), and increased short-circuit currents (Isc). Carbachol was more potent and more effective than McN. Muscarinic antagonists were used to define the muscarinic receptor involved. The pA2 values obtained with Schild plots were as follows: atropine 9.14, 4-DAMP 8.98, AFDX-116 6.71, and pirenzepine 7.12. Low concentrations of pirenzepine (10(-8) M), produced a rightward shift in the dose-response curve to McN, without inhibiting responses to carbachol. Thus the receptor subtype is clearly not an M2. As in other glandular systems, M3 receptors are present. Whether M1 receptors also exist requires better definition of receptor densities-reserves in this tissue. Carbachol induced net secretion of Na and Cl and converted a predominantly absorptive tissue to a secretory one.

(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethy↗
PubMed1990

Luminal responses to bradykinin on the isolated canine tracheal epithelium: effects of bradykinin antagonists.

We have tested the ability of several B2 antagonists on the responses of the open-circuited isolated canine tracheal epithelium to the luminal addition of Bradykinin (BK), Lys-BK, and substance P (SP). All three peptides produced biphasic changes in transmural potential difference (PD), an initial decrease (dip) followed by an increase (rise). The B2 antagonists D-Arg0 [Hyp3,Thi5,8,D-Phe7]BK (B5630) reversibly inhibited both the dips and the rise with IC50 values of 2.01 x 10(-8) and 1.54 x 10(-7) M, respectively. The responses to SP were unaffected even with high concentrations of the antagonist. Other antagonists tested [D-Phe1,7,Thi5,8]BK (B4158), [D-Phe2,7]BK (B4404), and [D-Phe7,Hyp8]BK (B5092) were ineffective.

Amino Acid Sequence↗
PubMed1990

A rapid method to determine proliferation patterns of normal and malignant tissues by H3 mRNA in situ hybridization.

A general method applicable for the determination of any mammalian tissue's proliferative pattern is described. This method determines the cellular mRNA level of a proliferation-dependent gene, histone H3, by in situ hybridization. The cell-cycle S-phase-specific expression of this highly conserved ubiquitous cellular gene, and the lack of it in resting cells, permits the unambiguous identification of cycling cells in any tissues, normal or diseased. This method can be conveniently coupled with routine biopsy and could be streamlined for a central laboratory with results obtainable in 2 days. Furthermore, this procedure works successfully on formalin-fixed paraffin-embedded sections, thus allowing retrospective studies of biopsies or autopsy materials.

Cell Cycle↗
PubMed1988

Luminal receptors for bradykinin on the canine tracheal epithelium: functional subtyping.

Luminal addition of bradykinin (BK) to the open-circuited canine tracheal epithelium produces a biphasic response in transmucosal potential difference (P.D.): a rapid, transient decrease (dip) followed by a subsequent, more sustained increase (rise), both phases being associated with an increase in conductance. We have attempted to characterise the receptor subtype mediating the bradykinin response. Lys-bradykinin (Lys-BK) elicited a similar response, and its EC50 as judged from concentration-response relations was similar to that of BK. Cross-tachyphylaxis between the two peptides confirmed a common receptor. Des-Arg9-BK (a B1-agonist) neither elicited a response nor inhibited responses to BK. The novel B2-antagonist [Thi6,9-D-Phe8]kallidin reversibly inhibited responses to both BK and Lys-BK. The rapid changes in P.D. (dips) were unaffected by Na+ removal, but were eliminated by replacing luminal Cl- with isethionate. Thus, BK, acting on B2-receptors, transiently increases anion permeability of the luminal membrane of the canine tracheal epithelium.

Animals↗
PubMed1987

Effects of TMB-8, a calcium antagonist, on transport properties of the isolated canine tracheal epithelium.

The effects of the putative intracellular Ca2+ antagonist, TMB-8 (8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate), on the canine tracheal epithelium were examined. Luminal addition reduced rapidly, but reversibly, the transmucosal potential difference and increased the resistance across the open-circuited epithelium. Under short-circuit conditions, the drug reduced stimulation by prostaglandin E2, forskolin, 8-bromo cyclic AMP, prostaglandin F2 alpha and A23187. Inhibition of prostaglandin E2 responses were accompanied by reversal of net Cl- fluxes produced by the agonist. The effects of TMB-8 were unaffected by increasing Ca2+ in the bathing solutions, and were not mimicked by procaine, nitrendipine, calmidazolium, compound 48/80 or trifluoperazine. W7 did, to a limited extent, produce similar responses, though the drug was more toxic, and the effects were irreversible.

1-Methyl-3-isobutylxanthine↗
PubMed1987

Luminal tachykinin receptors on canine tracheal epithelium: functional subtyping.

Luminal addition of tachykinins to the open-circuited canine tracheal epithelium produces a biphasic response in the transmucosal potential difference (PD). A rapid, transient decrease is followed by a subsequent rise, both phases being associated with changes in conductance. Concentration-response curves demonstrated the following orders of potency: substance P greater than physalaemin greater than eledoisin = kassinin for the tachykinins, and substance P greater than substance P-(4-11) greater than substance P-(6-11) using the C-terminal fragments. Both sequences are similar to those reported for the dog carotid artery. These observations were confirmed by cross-tachyphylaxis experiments. SP-O-methyl ester, a selective agonist for the SP-P (or NK-1) receptor, elicited identical responses, and exhibited cross-tachyphylaxis to substance P. Bradykinin produced similar luminal responses, though different receptors are involved, since no cross-tachyphylaxis was observed between bradykinin and the tachykinins.

Animals↗