Putative physiological significance of vasopressin V1a receptor activation in rat pituicytes.

Physiological stimuli operative during, for example, dehydration or lactation, induce neurohypophysial astrocytes (pituicytes) to undergo reversible morphological changes, which in turn may modulate the release of vasopressin and oxytocin. To study the molecular mechanisms of this morphological plasticity, we used primary cultures of rat pituicytes. During stimulation with adenosine, pituicytes become stellate, which is characterized by a round, phase-bright soma and complex arborization, implying major cytoskeletal modifications. Following addition of vasopressin or oxytocin, stellate pituicytes revert to a flat shape. The effects of both hormones are mediated by V(1a) receptor activation, which also induces biphasic Ca(2+) (i) signals in pituicytes. Stellation reversal requires Ca(2+)-dependent activation of Cdc42, a small GTPase known to impact on the cytoskeleton. V(1a) receptor activation by vasopressin or oxytocin also stimulates [(3)H]taurine efflux from cultured pituicytes. As taurine inhibits vasopressin output from neurohypophysial terminals, we postulate a negative-feedback mechanism whereby secreted vasopressin limits its own availability. This stop signal might be reinforced by shape changes elicited by vasopressin in pituicytes. These results support the concept that, during specific physiological states, pituicyte V(1a) receptor activation modulates the release of neurohypophysial hormones.

Gastrin effects on isolated rat enterochromaffin-like cells following long-term hypergastrinaemia in vivo.

The enterochromaffin-like (ECL) cells play an important role in the regulation of gastric acid secretion. They respond to gastrin by a prompt increase in histamine secretion, an effect which is mediated by the CCK-(B)/gastrin receptor acting through the IP(3)/DAG pathway. In the rat, long-term treatment with acid secretion inhibitors induces hypergastrinaemia which, in turn, results in ECL cell hypertrophy and hyperplasia. The aim of the present study was to evaluate various functional parameters in acutely isolated rat ECL cells, following long-term hypergastrinaemia in vivo. Rats were treated with vehicle or a supramaximal daily dose of omeprazole for more than 10 weeks to ensure ECL cell hyperplasia. ECL cells were isolated from vehicle-treated animals and 24, 72 and 120 h after the last dose of omeprazole. The functional activity of the acutely isolated ECL cells was determined by measuring gastrin-and forskolin-induced histamine secretion. Changes in cytosolic free calcium upon gastrin stimulation were monitored by digital video imaging. ECL cells successively regained their ability to respond to gastrin following long-term hypergastrinaemia, reaching close to vehicle-treated levels 120 h after the last dose of omeprazole. In the rat, the response pattern of the ECL cells appears to normalise in parallel with the normalisation of plasma gastrin levels.