**Author details**

186 Prolactin

channels.

secretion in lactotropes.

through actions blocking electrical activity.

release parallel with an activation of the sensitive pathways are affecting the PRL release

The physiology of pituitary cells reflecting to suckling stimulus or separation from pups, controlled by various concentrations of DA: due to suckling stimulus with low dose of DA to PRL release or exhibit dose-dependent inhibitory effect. This experimental model (nonsuckled *versus* suckled) serves to demonstrate manipulations on concentrations of DA or receptors of DA *in vivo* or *in vitro* moreover, able to distinguish between ligand dissociation, and stimulation-induced elevation of PRL release. The suckling-induced desensitization/sensitization of pituitary cells is manifested at the cellular level by an increase of subpopulation of those cells less/ more sensitive to high/low dose ranges of DA. The receptor mediated intracellular mechanisms leading to these suckling-induced changes in DA responsiveness of lactotrophs is still not fully understood. It is possible that DA modulates the inputs in a biphasic manner: at low concentrations DA activates D1-like receptors, but higher concentrations activate the D2-like receptors resulting in inhibition. The receptorial desensitization or "tolerance" is based on the mechanisms, in which ligands of G-protein-coupled receptors (GPCRs) can promote specific intracellular signaling adaptation mechanisms parallel with the internalization process of the receptors. Estradiol up-regulates the GIRK channel subunits and controls the functional activation of the D2R-GIRK pathway on mammotrop cells for the DA action. The negative membrane potential "primes" the lactotroph population by removing inactivation of voltage-gated Ca2+

The intracellular mechanisms of DA activation connected to D2 receptors and G-proteins coupled subunits to control the cAMP levels and various ion channels: triggering potassium current influences voltage-activated calcium and potassium currents. Most of these plasma membrane channels have been characterized, but the mechanism connected to Ca2+ dependent action potentials and pacemaking activity is still not fully understood. The cAMP signaling pathway is probably in control of pacemaking, voltage-gated Ca2+ influx and PRL release is a PKA-independent mechanism. The parallel activation of PTX-sensitive and insensitive pathways are affecting the PRL release through changes in electrical activity or modulate voltage-gated calcium channels. A specialty of these "active" lactotroph cells that this voltage-gated calcium influx resulting in an organized superimposition of APs, so called "plateau-bursting" action potentials that generate high amplitude calcium signals triggers

The complexity and diversity of intercellular and paracellular communication suggests a common theory of a "third messenger" system: phosphorylation of the appropriate target or substrate proteins controlled by the activities of phosphorylating PKs and dephosphorylating by protein phosphatases (PPs). Significance of dephosphorylation has been already demonstrated in the CNS, signaling through the neurotransmitter receptors and ion channels, but role of PPs has been still left some uncertainty. In recent years efforts have been made to understand the role of protein phosphorylation-dephosphorylation in

processing extracellular signals to mediate secretory functions.

György M. Nagy *Neuromorphological and Neuroendocrine Research Laboratory Department of Human Morphology Hungarian Academy of Sciences and Semmelweis University, Budapest, Hungary* 

Viktória Reinhoffer *Neuromorphological and Neuroendocrine Research Laboratory Department of Human Morphology, Semmelweis University, Budapest, Hungary* 

Márk Oláh *Department of Human Morphology, Semmelweis University, Budapest, Hungary* 

Miklós Vecsernyés *Faculty of Pharmacy, University of Debrecen, Debrecen, Hungary* 

Béla E. Tóth *Director at Academic Research Consulting Group* 
