In vivo labeling of L-type Ca2+ channels by fluorescent dihydropyridines: evidence for a functional, extracellular heparin-binding site.

We have synthesized and characterized fluorescently labeled dihydropyridines (DHPs) as probes for L-type Ca2+ channels. Racemic as well as (+)- and (-)-1,4-dihydro- 2,6-dimethyl-4-(2-trifluoromethylphenyl)-3,5-pyridinecarboxylic acid 2-(aminoethyl)ethyl ester hydrochlorides were coupled to boron dipyrromethane (Bodipy) derivatives. (4,4-Difluoro-5,7-dimethyl-4-bora-3a,4a-diaza)-3- (s-indacene)propionic acid (DMBodipy)-DHP and (4,4-difluoro-7-styryl-4-bora-3a,4a-diaza)-3-(s-indacene+ ++)propionic acid (STBodipy)-DHP have Kd values in the nanomolar range for membrane-bound or partially purified skeletal muscle and for neuronal L-type Ca2+ channels.

A unique fluorescent phenylalkylamine probe for L-type Ca2+ channels. Coupling of phenylalkylamine receptors to Ca2+ and dihydropyridine binding sites.

The first fluorescently labeled phenylalkylamine, DMBODIPY-PAA (5-(3-[3-(4,4-difluoro-5,7-dimethyl-3a, 4a-diaza-4-bora-indacen-3-yl)propionamido] phenethyl-N-methylamino)-2-isopropyl-2-(3,4,5-trimethoxyphenyl)-valer onitrile) has been introduced for L-type Ca2+ channel research. DMBODIPY-PAA binds reversibly to L-type Ca2+ channels purified from rabbit skeletal muscle microsomes by wheat germ agglutinin-Sepharose chromatography. In this preparation DMBODIPY-PAA labels 412 pmol of phenylalkylamine receptors/mg of protein with a Kd of 6.

Mitochondrial Ca2+ antagonist binding sites are associated with an inner mitochondrial membrane anion channel.

The inner mitochondrial membrane contains specific Ca2+ antagonist binding sites unrelated to the L-type Ca2+ channel. The mitochondrial 1,4-dihydropyridine (DHP) and phenylalkylamine sites are reciprocally allosterically coupled, require anions (e.g.

Replenishment of AI-doses with oestrogens in physiological amounts: effect on sow prolificacy in a field trial.

Basing on results about physiological functions of seminal oestrogens in the genital tract of sows, the effects of an oestrogen replenishment to AI-doses were investigated in a field trial. Each ejaculate was split into two halves, which were either diluted to normal AI-doses (controls, n = 353) or diluted and replenished with oestrogens in physiological amounts (n = 384). Insemination by qualified technicians led to an improvement of the pregnancy rate (82.

Stereoselective hemodynamic effects of (R)-and (S)-propranolol in man.

In a randomized, double-blind, placebo-controlled, cross-over study 24 healthy volunteers were examined before and 2 h after oral administration of 80 mg (R,S)-, 40 mg (R)- and 40 mg (S)-propranolol.HCl; 8 of them received placebo in an additional run. During exercise on a bicycle ergometer and a rest period the rate pressure product was decreased by 80 mg (R,S)-propranolol.