Three-dimensional analysis of the heart function and effect cholinergic agonists in the cockroach Gromphadorhina portentosa.

Many relevant aspects of mammal's cardiac physiology have been mainly investigated in insect models such as Drosophila melanogaster and Periplaneta americana. Cardiac function has been poorly studied in the cockroach Gromphadorhina portentosa, which has some advantages for experimental purposes such as an easier culture, bigger organs and a robust physiology. On the other hand, the study of cardiac physiology in insects has been largely improved since the arrival of digital imaging technologies for recording purposes. In the present work, we introduce a methodology of video recording coupled to an isotonic transducer for a three-dimensional analysis of the heart and intracardiac valves of G. portentosa. We used this methodology for assessing the physiological responses of the cockroach heart upon the application of different cholinergic neurotransmitters (acetylcholine, nicotine and muscarine). We recorded in detail the relationship between intracardiac valves movement, hemolymph flow, diastole and systole. Acetylcholine and nicotine induced a biphasic effect on the cardiac frequency. Acetylcholine increased the diastolic opening. Nicotine at high concentration caused paralysis. Muscarine induced no major effects. These findings suggest a combined action of cholinergic agonists for a finely tuned the cardiac frequency, intracardiac valves function and cardiac cycle.

ß-Adrenoceptor Blockade for Infantile Hemangioma Therapy: Do ß3-Adrenoceptors Play a Role?

Infantile hemangiomas (IH) are frequent (4-5% of the childhood population) benign vascular tumors that involve accumulation, proliferation, and differentiation of aberrant vascular cells. Typically, IH are innocuous and spontaneously disappear, but they represent a potential risk for harmful effects in the body (e.g., permanent disfigurement) and health (e.g., ulcerations) in some patients. From a serendipitous discovery, the nonselective ß-adrenoceptor blocker propranolol (which blocks ß1-adrenoceptors, ß2-adrenoceptors, and ß3-adrenoceptors) emerged as an alternative therapy to treat this pathology and it quickly became a first-line treatment for IH. Nevertheless, its specific mechanisms of action remain thus far unknown. In this respect, several studies have suggested that ß1-adrenoceptors and ß2-adrenoceptors play a role in proliferative and angiogenic mechanisms. However, current basic research studies suggest that ß3-adrenoceptors could be also involved. Notably, ß3-adrenoceptors stimulate multiple intracellular pathways related to vascular function (e.g., blood flow, angiogenesis, etc.). This review compiles some lines of evidence suggesting that ß3-adrenoceptors may: (1) play a role in the pathophysiology of IH and (2) represent a potential therapeutic target for IH treatment. Hence, clinical evidence is mandatory to decide whether incorporation of ß3-adrenoceptor blockers into the therapeutic armamentarium may increase effectiveness in the treatment of IH and other vascular anomalies.

Some Prospective Alternatives for Treating Pain: The Endocannabinoid System and Its Putative Receptors GPR18 and GPR55.

Background: Marijuana extracts (cannabinoids) have been used for several millennia for pain treatment. Regarding the site of action, cannabinoids are highly promiscuous molecules, but only two cannabinoid receptors (CB1 and CB2) have been deeply studied and classified. Thus, therapeutic actions, side effects and pharmacological targets for cannabinoids have been explained based on the pharmacology of cannabinoid CB1/CB2 receptors. However, the accumulation of confusing and sometimes contradictory results suggests the existence of other cannabinoid receptors. Different orphan proteins (e.g., GPR18, GPR55, GPR119, etc.) have been proposed as putative cannabinoid receptors. According to their expression, GPR18 and GPR55 could be involved in sensory transmission and pain integration. Methods: This article reviews select relevant information about the potential role of GPR18 and GPR55 in the pathophysiology of pain. Results: This work summarized novel data supporting that, besides cannabinoid CB1 and CB2 receptors, GPR18 and GPR55 may be useful for pain treatment. Conclusion: There is evidence to support an antinociceptive role for GPR18 and GPR55.