pituitrin and 1-4-dihydropyridine

The effects of dihydropyridine ligands on the electrically evoked release of neurohypophysial hormones from isolated, rat neurointermediate lobes were investigated as a function of all combinations of two pulse widths (0.2 and 2 ms) and three stimulation frequencies (6.5, 13 and 30 Hz). The dihydropyridine agonist (S)-(+)-202-791 potentiated concentration dependently the release of both oxytocin and vasopressin at a pulse width of 2 ms and a frequency of 6.5 Hz. This effect of (S)-(+)-202-791 was abolished by the antagonist (-)-nitrendipine and stereospecifically by (R)-(-)-202-791 (only vasopressin). The antagonist (R)-(-)-202-791 alone inhibited the release of oxytocin at 13 Hz and 2 ms. The results presented show that the effects of the dihydropyridine ligands are dependent on the stimulation conditions, and thus demonstrate that the entry of Ca2+ through the dihydropyridine sensitive L-type Ca2+ channel is associated with electrically evoked release of neurohypophysial hormones under certain conditions.

Topics: Animals; Calcium Channel Agonists; Calcium Channel Blockers; Dihydropyridines; Electric Stimulation; Electrophysiology; Female; Ligands; Nicotinic Acids; Nitrendipine; Oxadiazoles; Oxytocin; Pituitary Gland, Posterior; Radioimmunoassay; Rats; Rats, Sprague-Dawley; Stereoisomerism; Structure-Activity Relationship; Vasopressins

The properties of the Ca2+ channels mediating transmitter release in vertebrate neurons have not yet been described with voltage-clamp techniques. Several types of voltage-dependent Ca2+ channels are known to exist on neuronal somata, but the small size and inaccessibility of most vertebrate nerve endings have precluded direct characterization of the presynaptic channels. However, large nerve endings, which release the peptides oxytocin and vasopressin in a Ca2(+)-dependent manner, can be dissociated from the rat neurohypophysis. Using both single-channel and whole-cell patch-clamp techniques, we have characterized two types of Ca2+ channels that coexist in these terminals. One is a large-conductance, high-threshold, dihydropyridine-sensitive channel that contributes a slowly inactivating current. The second is a smaller conductance channel, which is also activated at high thresholds, but underlies a rapidly inactivating, dihydropyridine-insensitive current. Both types of Ca2+ channels may participate in the peptide release process.

Topics: Action Potentials; Animals; Calcium; Calcium Channels; Dihydropyridines; Ion Channel Gating; Male; Nerve Endings; Oxytocin; Pituitary Gland, Posterior; Rats; Vasopressins