Parathormone secretion

All the pharmacological and behavioural effects elicited by dopamine agonists and antagonists in the brain can only be explained if such an interaction occurs at the level of the dopamine receptor (D2 receptor site) the site still remains in search of a function. Bovine parathyroid cells were reported to possess dopamine sites which should be involved in the control of parathormone secretion. However, the very poor pharmacological characterization and the lack of in vivo evidence do not allow to assess the dopaminergic nature of this hormone secretion. Dopamine-sensitive adenylate cyclase is thus not a receptor directly implicated in the dopaminergic neurotransmission it is an enzyme which could have an important role in the control of long term metabolic effects such as the synthesis of neuronal constituents. 

How the problem arises whether or not the dopamine-sensitive adenylate cyclase (D site) (2) also answers these criteria or other criteria which justify it being called a dopamine receptor like the D2 receptor site 15-8). The purpose of the present paper is to discuss this problem especially with regard to parathormone secretion. Special attention will be paid to the pharmacological characterization of this hormone secretion. 

ADTN and other dopamine agonists mimicked this effect which was antagonized by a- and B-flupenthixol, the a-isomer being 100 times more potent. In a similar way, dopamine caused a rapid 20-30-fold increase in cellular cAMP in dispersed bovine parathyroid cells. The potency of a series of dopaminergic agonists and antagonists on adenylate cyclase activity paralleled the effects of these ligands on CAMP accumulation and parathormone secretion (16). It was concluded that bovine parathyroid cells possess dopamine sites which are involved in the control of parathormone secretion. 

Compounds which can regulate (+) or not (-) cAMP production and parathormone secretion in parathyroid cells... 

More intriguing is the fact that the parathormone secretion occurs in the absence of dopamine what dopamine is doing, is to enhance a phenomenon already present this is also at variance with the normal physiological response to a neurotransmitter which is generally an all or none process. 

In fact the most important point concerns the very poor pharmacological characterization of the cAMP formation enhanced by dopamine and of the parathormone secretion. Firstly, apomorphine is much less potent than dopamine, a fact which is not compatible with what we know from pharmacological, behavioural and even biochemical studies (3,4 7) It is believed that apomorphine is a partial antagonist, but this has never been found in in vivo conditions. The higher potency of apomorphine is also reflected by its high affinity in %-haloperidol and 3H-spiperone binding. 

Only such an analytical approach can decide whether the control of the parathormone secretion involves a dopaminergic receptor. 

In my opinion, one may assume a priori that these criteria will not be fulfilled first, if the dopamine-sensitive adenylate cyclase was really involved in the parathormone secretion, the patients treated with neuroleptics and especially with the most potent drugs on the sites (phenothiazine and thioxanthene derivatives) would have normally revealed marked changes in their parathormone secretion, just like as is the case for the prolactin secretion in fact such changes have never been observed secondly, a recent report clearly indicates that the injection of dopamine in man does not modify parathormone secretion although a marked decrease in prolactin was observed (21). There is no receptor without physiological response the study of receptor requires a multidisciplinary approach. 

Control of Parathormone Secretion 347 Effect of Parathormone Hyperparathyroidism 350... 

In contrast to the secretion of other endocrines, which is controlled by various hormones, parathormone secretion is controlled solely by the calcium level in the blood. 

Conclusive evidence for the control mechanism of parathormone secretion has been obtained by experiments done on the thyroid-parathyroid preparation of the dog. In these experiments, the thyroid-parathyroid preparation is first perfused with calcium deficient blood, then the perfusate is injected intravenously to parathyroidectomized dogs. The injected dogs develop hypercalcemia and phosphaturia, indicating that perfusion of the parathyroids with low calcium levels stimulates parathormone secretion. It is not known whether the stimulated parathyroid synthesizes new hormone or releases existing parathormone. However, the crude parathyroid extracts of parathyroid-thyroid perfused with low calcium levels contained a new factor separable from the classical parathormone. The reciprocal experiment in which calcium-rich blood is used to perfuse the thyroid-parathyroid preparation leads to hypocalcemia in the animals injected with the perfusate. 

A peritoneal lavage technique was developed which permitted study of the effect of calcium and phosphate on the parathyroid. Parathyroid activity is measured by counting the development of osteoblasts in bone. Using calcium-free and phosphate-free lavage, investigators established that the calcium levels of serum control parathyroid secretion directly, and that any effect of the phosphate is indirect on parathormone secretion. 

If the level of parathormone is to be maintained constant in blood, as suggested by the feedback mechanism, then a pathway for parathormone breakdown must be available. It is not known where and how parathormone is destroyed. The liver is assumed to participate in parathormone breakdown because transplantation of parathyroid into the spleen prevents parathormone secretion. But such an experiment does not exclude the participation of the spleen in parathormone breakdown. 

Parathormone, secreted by the parathyroid gland, is the largest polypeptide analyzed at present. Its molecular weight of 8500 brings it pretty close to that of proteins. 

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