Biomaterial Database

Characterization of dopamine and alpha-adrenergic receptors in human prolactin-secreting adenomas with [3H]-dihydroergocryptine. 1985

J S Ramsdell, and C L Bethea, and R B Jaffe, and C B Wilson, and R I Weiner

One tenable hypothesis for the etiology of the development of prolactin-secreting adenomas is that a decrease in inhibitory dopaminergic regulation leads to increased lactotroph proliferation. Dopamine receptors have been repeatedly characterized on prolactin-secreting adenomas using labelled antagonists as ligands; however, no data are available on characterization of the receptor with a dopaminergic agonist. An agonist was utilized as the radioligand in the present study to permit the direct comparison of the pharmacological characteristics of the binding site with the biological response, the inhibition of prolactin secretion. This comparison has never been reported in tissues from the same species. Binding of the dopamine agonist and alpha-adrenergic antagonist [3H]-dihydroergocryptine ([3H]-DHE) to particulate fractions of surgically resected human prolactin-secreting adenomas was high affinity, monophasic, and saturable. Careful characterization of the [3H]-DHE binding by competitions with a large number of dopaminergic and alpha-adrenergic agents revealed the presence of both dopaminergic and alpha-adrenergic binding sites. The presence of a saturable, high affinity alpha-adrenergic binding site was confirmed with the specific alpha-adrenergic antagonist [3H]-WB4101 as a radioligand. Although the rank order of potency for dopaminergic compounds to compete for [3H]-DHE binding was consistent with an interaction with a dopamine receptor, the inhibitory constants (Ki) calculated from the competitions were higher than expected at an anterior pituitary dopamine receptor. This appeared to be due to the lower affinity of these agents at the alpha-adrenergic sites. The observed potency of dopaminergic compounds was inversely related to the number of alpha-adrenergic sites.(ABSTRACT TRUNCATED AT 250 WORDS)

UI	MeSH Term	Description	Entries
D008297	Male		Males
D008875	Middle Aged	An adult aged 45 - 64 years.	Middle Age
D010911	Pituitary Neoplasms	Neoplasms which arise from or metastasize to the PITUITARY GLAND. The majority of pituitary neoplasms are adenomas, which are divided into non-secreting and secreting forms. Hormone producing forms are further classified by the type of hormone they secrete. Pituitary adenomas may also be characterized by their staining properties (see ADENOMA, BASOPHIL; ADENOMA, ACIDOPHIL; and ADENOMA, CHROMOPHOBE). Pituitary tumors may compress adjacent structures, including the HYPOTHALAMUS, several CRANIAL NERVES, and the OPTIC CHIASM. Chiasmal compression may result in bitemporal HEMIANOPSIA.	Pituitary Cancer,Cancer of Pituitary,Cancer of the Pituitary,Pituitary Adenoma,Pituitary Carcinoma,Pituitary Tumors,Adenoma, Pituitary,Adenomas, Pituitary,Cancer, Pituitary,Cancers, Pituitary,Carcinoma, Pituitary,Carcinomas, Pituitary,Neoplasm, Pituitary,Neoplasms, Pituitary,Pituitary Adenomas,Pituitary Cancers,Pituitary Carcinomas,Pituitary Neoplasm,Pituitary Tumor,Tumor, Pituitary,Tumors, Pituitary
D011388	Prolactin	A lactogenic hormone secreted by the adenohypophysis (PITUITARY GLAND, ANTERIOR). It is a polypeptide of approximately 23 kD. Besides its major action on lactation, in some species prolactin exerts effects on reproduction, maternal behavior, fat metabolism, immunomodulation and osmoregulation. Prolactin receptors are present in the mammary gland, hypothalamus, liver, ovary, testis, and prostate.	Lactogenic Hormone, Pituitary,Mammotropic Hormone, Pituitary,Mammotropin,PRL (Prolactin),Hormone, Pituitary Lactogenic,Hormone, Pituitary Mammotropic,Pituitary Lactogenic Hormone,Pituitary Mammotropic Hormone
D011942	Receptors, Adrenergic, alpha	One of the two major pharmacological subdivisions of adrenergic receptors that were originally defined by the relative potencies of various adrenergic compounds. The alpha receptors were initially described as excitatory receptors that post-junctionally stimulate SMOOTH MUSCLE contraction. However, further analysis has revealed a more complex picture involving several alpha receptor subtypes and their involvement in feedback regulation.	Adrenergic alpha-Receptor,Adrenergic alpha-Receptors,Receptors, alpha-Adrenergic,alpha-Adrenergic Receptor,alpha-Adrenergic Receptors,Receptor, Adrenergic, alpha,Adrenergic alpha Receptor,Adrenergic alpha Receptors,Receptor, alpha-Adrenergic,Receptors, alpha Adrenergic,alpha Adrenergic Receptor,alpha Adrenergic Receptors,alpha-Receptor, Adrenergic,alpha-Receptors, Adrenergic
D011954	Receptors, Dopamine	Cell-surface proteins that bind dopamine with high affinity and trigger intracellular changes influencing the behavior of cells.	Dopamine Receptors,Dopamine Receptor,Receptor, Dopamine
D004088	Dihydroergotoxine	A mixture of three different hydrogenated derivatives of ERGOTAMINE: DIHYDROERGOCORNINE; DIHYDROERGOCRISTINE; and DIHYDROERGOCRYPTINE. Dihydroergotoxine has been proposed to be a neuroprotective agent and a nootropic agent. The mechanism of its therapeutic actions is not clear, but it can act as an alpha-adrenergic antagonist and a dopamine agonist. The methanesulfonate salts of this mixture of alkaloids are called ERGOLOID MESYLATES.	Co-Dergocrine,Ergot Alkaloids, Hydrogenated,Dihydroergotoxin,Alkaloids, Hydrogenated Ergot,Hydrogenated Ergot Alkaloids
D004146	Dioxanes	Compounds that contain the structure 1,4-dioxane.
D004298	Dopamine	One of the catecholamine NEUROTRANSMITTERS in the brain. It is derived from TYROSINE and is the precursor to NOREPINEPHRINE and EPINEPHRINE. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of receptors (RECEPTORS, DOPAMINE) mediate its action.	Hydroxytyramine,3,4-Dihydroxyphenethylamine,4-(2-Aminoethyl)-1,2-benzenediol,Dopamine Hydrochloride,Intropin,3,4 Dihydroxyphenethylamine,Hydrochloride, Dopamine
D005260	Female		Females