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Adenosine is involved in classic pre-conditioning (PC) in most species, acting through especially adenosine A1 and A3 receptors. We studied whether the adenosine A1 receptor (A1R) was important for remote, delayed adaptation to ischaemia using a mouse with targeted deletion of the A1R gene.Remote, delayed adaptation was evoked by brain ischaemia (BIPC) through bilateral ligation of the internal carotid arteries. Through microdialysis probes placed in the brain and the abdominal aorta, we found that plasma adenosine increased following carotid artery ligation. Twenty-four hours after ligation, hearts were isolated, Langendorff perfused and subjected to 40 min global ischaemia and 60 min reperfusion. Hearts from sham operated and BIPC animals either with (A1R+/+) or without (A1R−/−) the gene for the adenosine A1R were compared with each other.In wild types, BIPC reduced infarct size and improved functional recovery during reperfusion, but BIPC did not protect hearts of A1R−/− mice. There were no significant differences between sham-operated A1R+/+ and A1R−/− in recovery of function or infarct size. The mitogen-activated protein kinases (MAPKs) extracellular signal-regulated protein kinase1/2 (ERK1/2), p38 and c-jun N-terminal kinase (JNK) were phosphorylated during reperfusion of sham treated hearts. The increase in ERK1/2 and p38 phosphorylation detected was attenuated in hearts of BIPC or A1R−/− animals.During BIPC adenosine acting on the A1R appears necessary for myocardial protection. MAPK signalling may possibly be involved in organ protection during the delayed phase of remote, delayed adaptation. [ABSTRACT FROM AUTHOR]

Apomorphine 0.001, 0.005, 0.05 and 0.1 mg/kg were given i.v. to conscious dogs and gastrin and insulin levels were measured in peripheral venous blood. The lowest dose of apomorphine (0.01 mg/kg) did not change gastrin levels but some times caused a decrease of insulin levels, whereas the higher doses (0.005-0.1 mg/kg) induced a dose dependent increase of both hormone levels. The peak shaped release responses appeared within a few minutes and the basal values were reached again within 20 to 30 min. Apomorphine within the dose range which induced a response of insulin and gastrin also caused nausea and vomiting. After pretreatment with haloperidol (0.1 mg/kg) no signs of sickness were observed and the response of gastrin to 0.01 and 0.05 mg/kg of apomorphine was almost completely blocked, whereas the insulin response to both these dose was inhibited to approximately 50%. We conclude that the release of gastrin and insulin can be activated by stimulation of dopaminergic receptors, the anatomical location of which is not clear. Possible sites for the dopaminergic receptors are the hypothalamic region or the vagal centres in the medulla oblongata.

Radioimmunoassay revealed gastrin-like immunoreactivity in extracts of the heart muscle from cat, guinea pig, rabbit and hog. The immunoreactivity was unevenly distributed, the highest levels being observed in extracts from the atria of the cat heart: in the right atrium approximately 1,000 pg/g or 450 pmol/kg and in the left atrium approximately 4,400 pg/g or 2,000 pmol/kg. In extracts from the cat atria the gastrin-like immunoreactivity was identified as Gastrin-17. The preponderant localization of gastrin to the atria is suggested to be due to the distribution of gastrin containing vagal fibres and nerve terminals in that area, even if a possible localization to specific receptors, Purkinje fibres etc. cannot be excluded. A modulating action on the vagal influence on the heart, either on neurotransmission or on the receptor level, or a direct (perhaps trophic) effect on biochemical processes in the muscle are suggested as possible biological functions of the heart gastrin.

Recent evidence suggests a regulatory role in the nervous system for somatomedins. The present study, using a somatomedin radioreceptorassay which primarily detects insulin-like growth factors 1 and 2, shows that somatomedins are widely distributed throughout the nervous system of the cat. Whilst somatomedins were present in all CNS regions, the highest concentration occurred in the hypothalamus followed by cerebral cortex. In the spinal cord, the dorsal roots contained twice the concentration found in the ventral roots. Activity was also present in the sympathetic ganglia, vagus nerve and sciatic nerves. Following electrical stimulation of the brachial and sciatic nerves somatomedins were released into perfusates from extirpated cut limbs. These findings suggest that somatomedins may be neuroregulatory hormones.

Cortisol levels were measured in peripheral plasma of conscious dogs after i.v. administration of apomorphine, a dopaminergic agonist, haloperidol, a dopaminergic antagonist, or apomorphine in combination with haloperidol. Apomorphine in a dose of 0.001 and 0.005 mg/kg did not cause any release of cortisol whereas 0.01 and 0.05 mg/kg caused a dose dependent and peakshaped increase of plasma cortisol levels from 20 to 30 and from 20 to 60 ng/ml respectively. Basal levels were reached again within 1 h. Haloperidol (0.1 mg/kg), when given alone, induced a continuous rise of plasma cortisol levels. After 60 min the levels were approximately 80 ng/ml and still tended to rise. If apomorphine (0.01 mg/kg) was given 30 min after the injection of haloperidol (0.5 mg/kg) no further effect of the apomorphine injections was observed. We therefore speculate that apomorphine activates central dopaminergic receptors which cause a release of ACTH from the pituitary into the circulation, which in turn stimulates the release of cortisol from the adrenals. The fact that not only apomorphine but also haloperidol stimulated cortisol release suggests a complex role or dopamine transmission involving different dopaminergic pathways as well as different dopamine receptors. It is also possible that injection of haloperidol induces a stress reaction in the dogs, which causes a release of cortisol from the adrenals.