Salsolinol and the peripheral sympathetic activity: the effects of hypophysectomy, adrenalectomy and adrenal medullectomy.

The endogenous isoquinoline salsolinol (SALS) is a recently identified prolactin (PRL) releasing factor, a selective and potent stimulator of PRL secretion both in vivo and in vitro. SALS decreased the peripheral tissue dopamine (DA) level dose dependently, consequently increased the NE/DA ratio, indicating reduced release of newly formed norepinephrine (NE) from sympathetic terminals. The aim of our study was to investigate the effect of adrenal medullectomy (MEDX), adrenalectomy (ADX) and hypophysectomy (HYPOX) on the action of SALS on the PRL secretion, and on the catecholamine concentration of the selected sympathetically innervated peripheral tissues (atrium, spleen, etc). The experiments were done in male rats of 200-300 g body weight kept in air conditioned room with regular lighting. We used high-pressure liquid chromatography with electrochemical detection (HPLC-EC) for measurement of NE and DA concentrations, and radioimmunoassay for prolactin measurement. In MEDX as well as in ADX rats, SALS (25 mg/kg i.p.) was able to reduce DA level and increase the NE/DA ratio. The changes of prolactin secretion (increase by SALS) were not affected either by ADX or MEDX. Therefore the presence of the adrenal gland is not required for the changes of prolactin secretion, nor for the reduction of peripheral sympathetic activity induced by SALS. Investigating the possible effect of pituitary hormones on the peripheral sympathetic system, the action of SALS has been tested in HYPOX rats. We have found that the effect of SALS on peripheral sympathetic terminals is not affected by HYPOX, consequently the role of pituitary hormones in the effect of SALS on the peripheral catecholamine metabolism may be excluded.

Effect of local (intracerebral and intracerebroventricular) administration of tyrosine hydroxylase inhibitor on the neuroendocrine dopaminergic neurons and prolactin release.

BACKGROUND AND PURPOSE: Hypothalamic dopamine (DA), the physiological regulator of pituitary prolactin (PRL) secretion, is synthesized in the neuroendocrine dopaminergic neurons that projects to the median eminence and the neurointermediate lobe of the pituitary gland. The rate-limiting step of DA biosynthesis is catalyzed by the phosphorylated, therefore activated, tyrosine hydroxylase (TH) that produces L-3,4-dihydroxy-phenylalanine from tyrosine. The aims of our present study were to investigate 1. the effect of local inhibition of the DA biosynthesis in the hypothalamic arcuate nucleus on PRL release, and to get 2. some information whether the phosphorylated TH is the target of enzyme inhibition or not. METHODS: A TH inhibitor, alpha-methyl-p-tyrosine was injected either intracerebro-ventricularly or into the arcuate nucleus of freely moving rats and plasma PRL concentration was measured. Immunohistochemistry, using antibodies raised against to native as well as phosphorylated TH were used to compare their distributions in the arcuate nucleus-median eminence region. RESULTS: Intracerebro-ventricular administration of alpha-methyl-p-tyrosine has no effect, unlike the intra-arcuatus injection of enzyme inhibitor resulted in a slight but significant elevation in plasma PRL. Parallel with this, the level of DA and DOPAC were reduced in the neurointermediate lobe while no change in norepinephrine concentration can be detected indicating a reduced biosynthesis of dopamine following TH inhibition. On the other hand, systematic application of the alpha-methyl-p-tyrosine that inhibits TH activity located in DA terminals of the median eminence and the neurointermediate lobe, resulted in the most significant elevation of PRL. CONCLUSION: Our results suggest that alpha-methyl-p-tyrosine administered close to the neuroendocrine dopaminergic neurons was able to inhibit only a small proportion of the TH. Moreover, it also indicate that the majority of the activated TH can be found in the axon terminals of dopaminergic neurons, therefore, the DA released into the pituitary portal circulation is synthesized at this site.