Increased myocardial contractility and enhanced exercise function in transgenic mice overexpressing either adenylyl cyclase 5 or 8.

Objective: ss-adrenergic receptors (ssARs) are powerful regulators of cardiac function in vivo, activating heterotrimeric G proteins and the effector molecule adenylyl cyclase (AC). Interestingly, cardiac-specific overexpression of different AC isoforms leads to variable changes in cardiac function. Whether AC overexpression affects intrinsic cardiac contractility in an isoform-specific fashion determining a change in exercise capacity is currently unknown.

Cyclic AMP compartmentation due to increased cAMP-phosphodiesterase activity in transgenic mice with a cardiac-directed expression of the human adenylyl cyclase type 8 (AC8).

Hearts from AC8TG mice develop a higher contractility (LVSP) and larger Ca2+ transients than NTG mice, with (surprisingly) no modification in L-type Ca2+ channel current (ICa,L) (1). In this study, we examined the cardiac response of AC8TG mice to beta-adrenergic and muscarinic agonists and IBMX, a cyclic nucleotide phosphodiesterase (PDE) inhibitor. Stimulation of LVSP and ICa,L by isoprenaline (ISO, 100 nM) was twofold smaller in AC8TG vs.

Augmentation of cardiac contractility with no change in L-type Ca2+ current in transgenic mice with a cardiac-directed expression of the human adenylyl cyclase type 8 (AC8).

The beta-adrenergic cascade is severely impaired in heart failure (HF), in part because of a reduction in the activity of the two dominant cardiac adenylyl cyclase (AC) isoforms, AC5 and AC6. Hence, cardiac-directed AC overexpression is a conceivable therapeutic strategy in HF. In this study, we explored the consequences at the cellular and organ level of a cardiac-directed expression of the human AC8 in the transgenic mouse line AC8TG.

Nicotine withdrawal syndrome: behavioural distress and selective up-regulation of the cyclic AMP pathway in the amygdala.

Nicotine addiction is a major public health issue. The use of laboratory animal models is a crucial tool in research aiming at understanding the pathophysiological mechanisms of nicotine dependence and at proposing new therapies. In rodents, cessation of nicotine exposure or administration of the nicotinic antagonist mecamylamine induces a nicotine withdrawal syndrome.

Novel, not adenylyl cyclase-coupled cannabinoid binding site in cerebellum of mice.

In this study we report data suggesting the presence of a non-CB1, non-CB2 cannabinoid site in the cerebellum of CB1-/- mice. We have carried out [(35)S]GTPgammaS binding experiments in striata, hippocampi, and cerebella of CB1-/- and CB1(+/+) mice with Delta(9)-THC, WIN55,212-2, HU-210, SR141716A, and SR144528. In CB1-/- mice Delta(9)-THC and HU-210 did not stimulate [(35)S]GTPgammaS binding.

Studies on the half life time of rat liver transfer RNA species.

The tRNA fraction, extracted from very high speed supernatant fluid, from livers of rats injected with 3H-orotic acid, attained maximum specific activity after a little over 24 hr and, thereafter, decayed with an apparent half life of 5 days. This behaviour of tRNA was indistinguishable from that of liver rRNA and the acid soluble pool. Chromatography of tRNA, doubly labelled during a period of short synthesis and of prolonged decay, on a BD cellulose column, indicated that individual tRNA species turn over at a constant rate with respect to one another.