Autoradiographic localization of peripheral [3H]-hydergine binding sites.

The anatomical distribution of the ergot derivative [3H]-hydergine (co-dergocrine mesylate) was analyzed by the use of an in vitro autoradiographic technique on frozen sections of rat heart, mesenteric and renal arteries, adrenal gland and kidney. In the heart, [3H]-hydergine was bound by atria and by myocytes of ventricles. In the arterial wall, the drug was bound primarily by the adventitia, by the adventitia-media border and by the intimal layer. The density of adventitial and adventitial-medial binding sites has an inverse relation with the diameter of mesenteric or renal vessels. In the adrenal gland, [3H]-hydergine was bound primarily by the medulla and, in lesser amounts, by the zona glomerulosa. In the kidney, the drug was localized within the arterial tree as well as in cortical tubules and in medullary collecting tubules. The above findings suggest that [3H]-hydergine is bound by various structures involved in the regulation of cardiovascular homeostasis. Interaction with these sites probably accounts for the antihypertensive action of hydergine.

Effect of prolonged co-dergocrine mesylate treatment on choline acetyltransferase levels in rat cerebral cortex after lesioning of the nucleus basalis magnocellularis (of Meynert).

The effects of monolateral lesions of the nucleus basalis magnocellularis (of Meynert) and of 1 or 4 weeks of co-dergocrine mesylate treatment (0.1 or 0.6 mg/kg) on choline acetyltransferase activity in rat frontal, parietal and occipital cortex were studied. According to the literature, ibotenic acid-induced lesions of the nucleus basalis magnocellularis cause a significant decrease in choline acetyltransferase activity in frontal and parietal cortex, but had no effect on enzyme activity in the occipital cortex or cortical areas controlateral to the lesion. Co-dergocrine administration caused, after 4 weeks of treatment, a dose related increase of choline acetyltransferase activity in the frontal and parietal cortex in the lesioned side. In contrast, it had no effect on the enzyme activity in the other cortical regions studied. The possible significance of the increased choline acetyltransferase activity elicited by co-dergocrine mesylate in cerebral cortex areas sensitive to nucleus basalis magnocellularis lesions is discussed.

Effects of long-term Hydergine administration on lipofuscin accumulation in senescent rat brain.

The effects of ageing and of 6 months of Hydergine treatment on lipofuscin deposition within the cytoplasma of pyramidal neurons of rat prefrontal cortex, hippocampus (fields CA1 and CA3) and of Purkinje neurons were assessed microfluorimetrically. No lipofuscin autofluorescence was detected in the nerve cell populations of 3-month-old rats, but lipopigment had accumulated in nerve cell bodies of 16-month-old animals and increased significantly thereafter in rats of 22 months of age. In 22-month-old rats, Hydergine administration (0.6 and 1 mg/kg p.o.) started at 16 months caused a significant dose-related decrease in lipofuscin accumulation within the cytoplasm of the various kinds of nerve cells examined.

Vasoactive intestinal polypeptide-sensitive cyclic adenosine monophosphate generating system in the rat portal vein.

The effect of vasoactive intestinal polypeptide (VIP) on the 3'-5'-cyclic adenosine monophosphate (cAMP) generating system in membrane particles of rat portal vein was studied. In the presence of 10 microM GTP, VIP increased the concentration of cAMP in a dose-dependent manner. The removal of endothelium had no effect on cAMP production elicited by VIP. alpha- and beta-adrenergic as well as muscarinic receptor blocking agents did not inhibit VIP-dependent cAMP increase. Also various peptides, structurally analogous to VIP or active on portal vein smooth muscle, had no effect on cAMP production elicited by VIP. The present data, combined with those reported in the literature of an active relaxation of portal vein smooth muscle by VIP, suggest the existence of functionally active VIP receptors coupled to the adenylate cyclase system in the rat portal vein.

Effect of dopamine on the cyclic adenosine monophosphate generating system in the rabbit internal carotid and middle cerebral artery.

The effect of in vitro addition of dopamine on the 3'-5'-cyclic adenosine monophosphate (cAMP) generating system of rabbit internal carotid and middle cerebral artery was studied. Dopamine increased cAMP levels in a dose-dependent manner in both arteries. The DA1-receptor antagonist SCH 23390 decreased the dopamine-elicited cAMP increase. On the contrary, the DA2-receptor antagonist L-sulpiride caused an increase in dopamine-dependent cAMP levels. The simultaneous addition of SCH 23390 and of L-sulpiride abolished any effect of dopamine on cAMP content. The DA2-receptor agonists bromocriptine and co-dergocrine decreased cAMP levels. The above findings indicate the existence in the rabbit internal carotid and middle cerebral artery of 2 types of dopamine receptors mediating respectively, the increase (DA1-effect) and the decrease (DA2-effect) of cAMP levels.

Metabolism of coronary vasculature in senescent rats--a histochemical study.

The effect of senescence on the metabolic profile of rat coronary arteries and arterioles was studied using enzyme histochemical techniques. In coronary arteries anaerobic metabolism predominates. In senescence an increase of adenosine triphosphatase (ATPase) occurred. The succinate dehydrogenase (SDH) and the respiratory chain metabolism marker NADH2-tetrazolium reductase (NADHD) showed an age-related decrease. Lactate dehydrogenase was unchanged. In the coronary arterioles, on the contrary, aerobic metabolism dominates. In senescence a significant decrease of NADHD and a moderate reduction of SDH and ATPase was observed. L-Carnitine administration significantly stimulated some enzymatic activities related to aerobic metabolism primarily at the arteriolar level.

Dopamine receptors mediating the stimulation and the inhibition of adenylate cyclase in rat prostate gland.

The effect of dopamine on the 3',5'-cyclic adenosine monophosphate (cAMP) generating system of membrane particles of rat prostate gland was studied. Dopamine increased the concentration of cAMP in a dose-dependent manner. The selective D1 receptor inhibitor SCH 23390 caused a decrease in dopamine-elicited cAMP levels. Any effect of dopamine on prostatic cAMP concentration was abolished by the simultaneous addition to the incubation medium of SCH 23390 and of the D2 receptor blocking agent (-)-sulpiride. Also the D2 receptor agonist bromocriptine decreased cAMP levels. The present data indicate the existence, in the rat prostate gland, of two types of dopamine receptors mediating, respectively, the activation (D1 effect) and the inhibition (D2 effect) of adenylate cyclase activity.

Autoradiographic localization of the dopaminergic agonist 3H-dihydroergotoxine within the male reproductive system.

By the use of combined radioreceptor binding and autoradiographic techniques, we analyzed the anatomical localization of the dopaminergic agonist 3H-dihydroergotoxine in tissue sections of rat male sex organs. The drug was bound by smooth muscle cells of the deferent duct, seminal vesicles and prostate gland as well as by the glandular tissue of seminal vesicles and prostate gland. These data allow us to hypothesize that the effect of dopaminergic agonists on male sexual function may be due, at least in part, to a direct interaction with dopamine receptors present in the reproductive organs.