Injection Of Forskolin Research Articles

Establishment of tracheal intubation model following post-cardiac arrest syndrome in rabbits

Objective To establish a less-damage method for tracheal intubation so as to improve the quality of post-cardiac arrest syndrome. Methods Thirty rabbits were divided into 3 groups of 10 rabbits each according to the random number table: group A receiving direct endotracheal intubation after anesthesia, Group B separation of cervical tissue and retrograde tracheal intubation after anesthesia and Group C percutaneous retrograde tracheal intubation after anesthesia. After the intravenous injection of forskolin, cardiac arrest was induced by endotracheal tube clamping. After 5 minutes of untreated arrest, conventional cardiopulmonary resuscitation was initiated. Changes in arterial pressure, occurrence of post-resuscition syndrome and survival time were examined in all groups. Results Groups A, B and C showed 40%, 60% and 80% success rate in cardiopulmonary resuscitation (P<0.01) and animal survival time of 23.4 hours (11.6-35.8 hours), 62.7 hours (29.4-88.6 hours) and 79.5 hours (40.9-118.2 hours) (P<0.01). Conclusions Percutaneous retrograde tracheal intubation is suitable to increase cardiopulmonary resuscitation rate and survival rate in rabbits with post-cardiac arrest. The model has good stability and repeatability and can be used for study of post-cardiac arrest syndrome. Key words: Trachea; Heart arrest; Rabbits

A cyclic AMP mechanism mediates the serotonin-induced increase in glutamic acid decarboxylase activity in the preoptic area and hypothalamus.

Previous studies have shown that the injection of 5-hydroxytryptamine (5-HT) into the third ventricle of rats on the afternoon of proestrus increases glutamic acid decarboxylase (GAD) activity in the preoptic area and the hypothalamus. In the present report we examine the adenylate cyclase-cyclic AMP (cAMP) system as mediator of that effect. The increase in GAD activity induced by intraventricular injection of 5-HT was completely blocked by injecting an antiserum against cAMP into the third ventricle 30 min earlier, whereas an injection of serum from normal rabbits was ineffective. On the contrary, activation of adenylate cyclase activity by intraventricular injection of forskolin increased GAD activity, an effect that was also blocked by anti-cAMP serum. Anti-cAMP serum also lowered GAD activity in the preoptic area and hypothalamus when injected on the morning of proestrus but not when injected in the afternoon, when the values of GAD activity were already low. The results suggest that a cAMP mechanism may be involved in the changes in preoptic-area and hypothalamic GAD activity such as the rise in enzyme activity induced by intraventricular injection of 5-HT.

Induction of tyrosine hydroxylase in the rat substantia nigra by local injection of forskolin

Forskolin (FSK) was locally injected into the substantia nigra (SN) of anesthetised rats. The day after injection (24 and 36 hr), tyrosine hydroxylase (TH) activity increased locally in this structure but remained unmodified in the ipsilateral caudate nucleus (CN). The amount of messenger RNA for TH (TH-mRNA) was also increased in the SN 24 hr after the injection. However, TH protein content was modified neither locally in the SN nor in the ipsilateral CN. In addition, the decrease of the ratio between dopamine and its first metabolite in the CN and the SN suggested a decreased activity of the dopaminergic nigral cells. The absence of increase of the protein synthesis in spite of the fact that TH-gene transcription was initiated could be the consequence of the inhibition of dopaminergic cells by the drug. These results confirm that, in vivo, TH induction is cAMP-dependent and demonstrate that the TH-gene activity is not strictly coupled to the activity of dopaminergic cells in the SN.

What constitutes a serotonergic neurone in the retina?

When exposed to exogenous serotonin, specific neurones in retinas from different species (guinea pig, rabbit, frog, pigeon and goldfish) take the amine up; these same neurones do not reveal endogenous serotonin following immunocytochemistry for the localization of the amine. The use of autoradiography and immunocytochemistry to localize the uptake of radioactive or unlabelled amine gives identical results, with the exception of the guinea pig retina, where a subset of horizontal-like cells specifically takes up a metabolite of [(3)H]serotonin (presumably produced in the extracellular space of the retina). This uptake is blocked specifically by N-acetyl-serotonin. After an intraocular injection of forskolin into the rabbit eye the serotonin content of the tissue is elevated and this is reflected in the demonstration of serotonin immunoreactivity associated with a subpopulation of amacrine cells. These cells correspond in size and position to the "indoleamine-accumulating cells" of the retina. Animals (goldfish, frog, pigeon) dark-adapted over a certain period manifest an elevated level of serotonin associated with their retinas compared with that in light-adapted animals. However, immunofluorescence histochemistry used to localize serotonin showed that the same neurones in the different retinas contain the amine, although the "fluorescence" was elevated in the dark-adapted retinas. In the light of the present data it is clear that what constitutes a "serotonergic" neurone cannot be restricted to the immunohistochemical demonstration of the amine. The evidence is persuasive for "serotonergic neurones" having the property to take up serotonin specifically by a high affinity transport process. What warrants serious consideration is whether this property is a characteristic of "serotonergic neurones" rather than the endogenous localization of serotonin without pharmacological pretreatment.

Morphological changes in pancreatic B-cells after intravenous administration of forskolin.

The morphological changes in rat pancreatic islets were studied after intravenous injection of forskolin (1.5 mg/kg), an activator of adenylate cyclase, to male Wistar rats. A high amount of insulin containing granules was observed on PAP immunostained paraffin sections. Ultrastructural study of islet B-cells demonstrated enlarged perinuclear space, dilated cisternae of rough endoplasmic reticulum and activated Golgi complex with numerous vesicles. The results suggest that intravenous administration of forskolin produces a modest increase of B-cell synthetic activity in the pancreatic islets of rats. It is assumed that forskolin affects pancreatic B-cells via increased cAMP.

Forskolin stimulates cyclic AMP synthesis, lowers intraocular pressure and increases outflow facility in rabbits.

The intracellular pathway by which beta-adrenergic agonists and antagonists affect aqueous humor dynamics involves the intracellular mediator, cyclic AMP. We have therefore tested the activity of forskolin, a direct activator of adenylate cyclase, in rabbits. Following a 15 min in vitro incubation in the presence of forskolin (15 microM) and isobutylmethylxanthine, a 10 fold increase in cyclic AMP was found in both rabbit iris-ciliary body and scleral-trabecular rings relative to controls. Following an intracameral injection of forskolin (10 micrograms) a time-dependent decrease in intraocular pressure was observed, which reached a mean decrease of 5 mm Hg at 4 hr in unanesthetized rabbits. Outflow facility was measured in anesthetized rabbits by constant pressure perfusion before injection and 1 hr after injection of either forskolin (10 micrograms) or control vehicle. Forskolin caused an approximate doubling of outflow facility (0.41 microliter/min/mm Hg) compared to the preinjection mean value. Control vehicle, ethyl alcohol, caused a statistically insignificant increase in outflow facility. At this concentration of forskolin, the integrity of the blood-aqueous barrier was normal as measured by protein and fluorescein entry into the aqueous humor. These results indicate that agents which directly activate adenylate cyclase are effective at increasing outflow facility and decreasing IOP.