On the VIP-ergic innervation of the uterotubal junction

Chronic ACTH treatment (3 IU/kg daily for 8 days) caused an increase in wet weight of the interscapular brown adipose tissue (ISBAT) in the rat without affecting the enzyme activities of the cardiac or skeletal muscles or of ISBAT. On the other hand, chronic β-blockade (alprenolol 10 mg/kg daily for 8 days) induced elevated activities in the oxidative enzymes of the ISBAT but not of the muscle tissues measured. Combined ACTH and alprenolol treatment also increased significantly the citrate synthase and malate dehydrogenase activities and protein concentration, but decreased the weight of ISBAT to normal. The results suggest that, although a direct antagonism between the β-blockers and ACTH has not been demonstrated, β-blockers can abolish the ACTH-induced weight gain of the ISBAT.     

The turnover of acetylcholine in ligated sciatic nerves of the rat

The accumulation of acetylcholine (ACh) and choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) activities proximal to a crush on rat sciatic nerves was investigated after superfusion of the nerves in situ with or without inhibitors of ACh synthesis and/or AChE. 9 h after crushing of nerves, the ACh-content of the 5 mm segment of nerve immediately proximal to the crush was increased from 37±5 to 80±4 pmol (mean ± SE), while ChAT-activity was increased to 112±10% and AChE-activity to 198±19% over that in non-ligated nerves. Superfusion of the nerves for 8 h with Krebs' bicarbonate medium had no effect on enzyme accumulations, but reduced the ACh content to 59±4 pmol. The presence of hemicholinium 3 (HC-3) (2×10^-5 M) in the superfusion medium reduced the ACh content markedly (to 17±2 pmol), but had no effect on enzyme accumulations at the crush. Adding eserine (10^-5 M) or soman (10^-6 M) to the superfusion medium increased ACh content to 133±8 pmol and 101±8 pmol, respectively, and markedly reduced AChE-activity; ChAT activity was not effected. Superfusion with a combination of HC-3 and eserine caused a marked reduction in ACh content compared with eserine alone; the effect was less with soman. The results are consistent with the view that the ACh which accumulates proximal to crush exists in a protective organelle, but that there is a continuous turnover of ACh due to leakage of ACh from the organelle, both during axonal transport and after accumulation.     

The recovery of noradrenaline in adrenergic nerve terminals of the rat after reserpine treatment

Tissue concentrations of endogenous noradrenaline in heart, submaxillary gland, and gastrocnemic muscle have been examined after one large dose of reserpine (10 mg/kg) to rats. After the initial depletion of the amine, the concentration started to rise between 24 and 36 h. For about one week thereafter the amine recovery proceeded comparatively fast, then the rate of the recovery slowed. Between the 4th and the 6th weeks there was a pronounced drop in the noradrenaline concentration in all three tissues, apparently beginning in the 4th week with a maximal decrease of about 20% in the 5th week after reserpine. Thereafter the concentrations increased to approach normal about 6 weeks after reserpine. These results are discussed in relation to the axonal down-transport of newly formed amine storage granules and to the life-span of these granules in the nerve terminals. The different parts of the noradrenaline recovery curve appeared to reflect the axonal down-flow of granules. A theoretical recovery curve was calculated, based on granular transport. This curve was similar to the observed recovery curve. The claim is made that the recovery of adrenergic function and noradrenaline levels after reserpine is due to a down-transport of newly formed, amine storage granules to the nerve terminals. There seems little need for the theory that the storage function reappears in old, reserpine-blocked granules, as a mechanism for noradrenaline recovery after a large dose of reserpine.     

The uptake and retention of [3H]noradrenaline in rat sciatic nerves after ligation

The uptake and retention of [³H]noradrenaline (³H-NA) was examined in sciatic nerves of albino rats. In the 1 cm part of nerve proximal to a 12 hr ligation the uptake and retention of exogenous noradrenaline was about 4 times the uptake in 1 cm of normal unligated nerves. Treatment with reserpine 10 hr before killing caused a marked decrease in the estimated amount of ³H-NA, while injection of nialamide 15 min before ³H-NA administration in ligated, reserpine-treated animals caused a somewhat larger uptake and retention of ³H-NA in the nerve part above the ligation. Protriptyline, a blocker of the “membrane pump”, was approximately 3 times less effective in 12 hr-ligated nerves than in unligated nerves, indicating a reduced efficiency of the “membrane pump” in the distended axons above a ligation.     

The involvement of intramural nerves in cholera toxin induced intestinal secretion

In previous reports we have suggested that nervous reflexes are involved in the pathophysiology of cholera secretion and that these nervous reflexes involve a cholinergic synapse and a neuron with vasoactive intestinal polypeptide (VIP) as neurotransmitter. These proposals were further analyzed in this study. Tetrodotoxin (TTX) and lidocaine applied on the serosal surface inhibited cholera secretion in segments of rat small intestine. Fluid absorption in control rats was not significantly changed. Hexamethonium given i. v. decreased cholera secretion in the cat. No additional inhibition of cholera secretion was observed after giving TTX close i. a. Furthermore, the intestinal secretion evoked by VIP was not influenced by hexamethonium given i. v. or TTX given close i. a. The present observations support the hypothesis of a role for nervous reflexes in cholera secretion. The results suggest that at least a major part of the proposed nervous reflex(es) in cholera have a cholinergic synapse. Furthermore, the VIP-ergic neuron is situated “distal” to the cholinergic neuron in the reflex(es) closer to the effector cells.     

Recovery of noradrenaline in adrenergic axons of rat sciatic nerves after reserpine treatment

The recovery of noradrenaline in adrenergic axons of the rat sciatic nerve after a single dose of reserpine (10 mg/kg i.p.) has been studied in unligated nerves and nerves ligated for 6 h. In unligated nerves the recovery at 24 h after reserpine was about 14% of normal. The noradrenaline content then slowly rose to reach about normal concentrations 6–7 days after reserpine injection. In nerves ligated 6 h before death, about 8·0 ng of noradrenaline accumulated proximal to the ligation in normal animals. At 6 and 12 h after reserpine about 4% of normal amounts of noradrenaline were found. Thereafter the amount of accumulated noradrenaline rapidly increased to about normal levels on day 2 after reserpine. At this time the content in unligated nerves was only about 45% of normal unligated nerve. On days 3–5 after reserpine, supranormal accumulations of noradrenaline were found (statistically highly significant), having a maximum at day 4 of about 145% of normal. At this time the noradrenaline content in unligated nerve was only about 80% of normal. The results may indicate an increased synthesis and increased rate of downtransport of amine storage granules during the early recovery phase after reserpine. This phenomenon may be part of a feed-back mechanism operating after depletion of the transmitter in the nerve terminals.     

Structural and functional ontogenetic development of the rat portal vein after neonatal 6-hydroxydopamine treatment

The importance of the adrenergic vasomotor nerve supply for the vascular ontogenetic development has been studied in the isolated portal vein preparation from rats, at 5–6 weeks of age, who had either been chemically sympathectomized by a series of postnatal 6-hydroxydopamine (6-OHDA) injections or been receiving the solvent alone. It was found that 6-OHDA treatment largely, but not completely, prevented the outgrowth of the terminal NA fluorescent ground plexus. Nevertheless, the media underwent a seemingly normal differentiation into two layers. Functionally, the portal vein from the 6-OHDA treated animals displayed weak and non-persistent myogenic spontaneous activity; sensitivity to exogenous noradrenaline (NA) was increased 3-fold and maximum stress was increased by 25 % as compared to control. Responses to transmural field stimulation were only obtained at high impulse rates and the maximum response was attenuated. Considering the very sparse adrenergic innervation following 6-OHDA they seemed surprisingly large, however, but since they were abolished by tetrodotoxin and by phenoxybenzamine responses are concluded to be neurogenic and adrenergic in origin. A singular attenuation of neurogenic responses by atropine was found in 6-OHDA treated vessels but not in controls. It is concluded that the adrenergic vasomotor nerve supply seems to exert some trophic influence during ontogenetic development but that the morphologic vascular development is largely governed by other, non-neurogenic mechanisms. As to functional development, 6-OHDA induced sympathectomy causes impaired development of phasic myogenic activity whereas maximum stress is augmented as is the tissue sensitivity to exogenous NA.     

The effect of propranolol on the serotonin concentration in the portal plasma after vagal nerve stimulation in the cat

Efferent cervical vagal nerve stimulation in the cat caused a marked increase of the portal plasma 5-HT concentration. This increase was more than two-fold within 15 min of stimulation. After cessation of stimulation portal plasma 5-HT returned to basal levels within 10 min. Treatment with the β-adrenoceptor antagonist propranolol, in various doses (0.1–2 mg/kg b.wt.), did not abolish but significantly reduced the response to vagal stimulation, particularly during the final part of the stimulation period. The results confirm the existence of a β-adrenoceptor-mediated release of 5-HT, but also suggest that other mechanisms for 5-HT release may be involved in the response on vagal nerve stimulation.     

The uptake of 5-hydroxytryptamine in endothelial cells cultured from the pulmonary artery in rats: A cytochemical study

Endothelial cells from the rat pulmonary artery were cultured and identified ultrastructurally and immunocytochemically by the presence of factor VIII antigens. Monolayers of cultured cells were treated according to the Hillarp-Falck technique and studied cytofluorimetrically to estimate intracellular serotonin (5-HT) levels. An uptake of 5-HT from the incubation medium was demonstrated at a concentration of 10^-3 M. However, after inhibition of monoamine oxidase (nalamide 5 × 10^-4 M) to prevent intracellular degradation of the amine an uptake could be demonstrated at 10^-5 M. The amine uptake into endothelial cells utilizes an active pumpmechanism, since it was effectively antagonized by either imipramine (10^-4 M) or ouabain (10^-5 M). These in vitro findings contrast earlier cytofluorimetric in vivo studies, where 5-HT uptake predominantly occurred in interstitial mast cells.