The pivotal role for voltage‐sensitive calcium channels in initiating synaptic transmitter release is undisputed, but it is only partly known to what extent the different subtypes contribute in vivo. Their importance for the dendritic release of dopamine has not been investigated in vivo previously. To evaluate comprehensively the relative importance of different voltage‐sensitive calcium channel subtypes for striatal dopamine release, and to further investigate the mechanism of dendritic dopamine release in the reticulate part of substantia nigra, dopamine was measured by in vivo microdialysis in the striatum or substantia nigra of awake rats. The calcium channel blockers nimodipine, ω‐conotoxin‐GVIA, ω‐agatoxin‐IVA, and neomycin were administered locally through the dialysis probes and compared with calcium‐free perfusion. Results indicate that dopamine release in the striatum is mainly dependent on N‐ and P/Q‐type channels, but the dendritic dopamine release in the substantia nigra is mediated mainly by some other calcium‐dependent mechanism, for example, calcium mobilization through T‐, O‐, or R‐type calcium channels. A portion of the dendritic release is calcium independent but can be inhibited partially by neomycin, which might suggest a role for inositol 4,5‐bisphosphate breakdown products.

Respiratory activity was studied in rats during light halothane anesthesia. Thyrotropin releasing hormone (TRH) and two TRH analogues: the desamidated form (TRH-OH) and gamma-butyrolactone-gamma-carbonyl-L-histidyl-L-prolinamide citrate (DN 1417) were administered intracerebroventricularly. TRH 0.5-5 micrograms induced a marked tachypnoea with a rapid onset and a duration of at least 20 min. DN 1417, a potent analogue of TRH with a very low TSH (thyroid stimulating hormone) releasing activity was more effective in stimulating respiratory frequency, while TRH-OH, regarded to have neither TSH releasing nor extra hypothalamic effects, at equimolar doses was unable to induce any changes in the respiratory pattern. When TRH was given into the fourth ventricle the dose response curve was slightly shifted to the left. In experiments employing the occluded breath technique, P0.1 was increased in the same magnitude as the mean inspiratory flow (VT/T1). The results also indicated an increase in the gain of the inflation reflex loop whereas the central bulbopontine setting for T1 and TTOT were not significantly changed. Local injection of TRH into the nucleus tractus solitarii induced a stimulation of respiratory frequency which was slower in onset compared to the response seen after injection into the lateral or fourth ventricles. Concomitantly to the respiratory changes, i.c.v. TRH injection induced a hypocarbia and an alkalosis. No changes in blood pressure or heart rate were seen. The respiratory stimulant effect of TRH could be potentiated by pretreatment with naloxone, methylatropine or a low dose of GABA. Haloperidol or propranolol did not significantly change the respiratory effects of TRH, while reserpine pretreatment seemed to blunt some of the ventilatory effects of TRH. It seems likely that TRH has few direct effects on brain stem neurones involved in the central regulation of respiration, but the main effects seem to be elicited in areas rostral to the brain stem. The respiratory stimulating effect of TRH is unrelated to TSH. Furthermore, other neurotransmitter systems might also be involved in modulation of the respiratory stimulation evoked by TRH.

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The importance of voltage-dependent sodium channels and different types of voltage-sensitive calcium channels for depolarisation-induced release of endogenous dopamine from dendrites and cell bodies in superfused guinea pig substantia nigra slices was investigated. The stimulatory effect of veratridine (10 microM) on dopamine release was only marginally attenuated in Ca(2+)-free medium but was completely blocked by tetrodotoxin (1 microM) and by the dopamine reuptake inhibitor GBR 12909 (10 microM). Low extracellular concentration of Na+ stimulated the dopamine release. Potassium-evoked dopamine release was completely Ca(2+)-dependent, not blocked by GBR 12909 and partially blocked by tetrodotoxin. Nifedipine (20 microM), omega-conotoxin GVIA (0.5 microM), penfluridol (5 microM), and Ni2+ (20 microM) had no effect, amiloride (1 mM) attenuated and neomycin (350 microM), and omega-agatoxin IVA (1 microM) almost totally blocked the potassium-induced dopamine release. The results suggest that veratridine released dopamine mostly by reversing the dopamine transporter. High concentrations of potassium induced release of nigral dopamine by opening of voltage-sensitive calcium channels of P/Q type but not L-type, N-type and probably not T-type. The depolarisation evoked by high concentrations of potassium seems to open voltage-sensitive calcium channels both by the depolarisation induced by potassium per se and by the secondary depolarisation induced by opening of voltage-dependent sodium channels.