Sensory origin of lobeline-induced sensations: a correlative study in man and cat

1. Intravenous injections of lobeline HCl into twenty-six normal young male human volunteers produced sensations of choking, pressure or fumes in the throat and upper chest at a mean threshold dose of 12 μg kg-1. 2. Reflex changes in breathing pattern usually appeared just before the sensations. Increasing the dose of lobeline increased the intensity of the sensations gradually until a dry cough appeared at a mean threshold dose of 24.3 μg kg-1. At these doses there was a mean difference of 0.3 s in the latencies for sensation and respiratory reflex; in four subjects there was no difference at all. 3. In cats anaesthetized with 35 μg kg-1 sodium pentobarbitone, injecting 25-67 μg kg-1 lobeline into the right atrium sensitized thirteen out of seventeen rapidly adapting receptors (RARs). In three out of four cats lobeline had no excitatory effect on the RARs in the absence of normal activity (i.e. when it was injected while artificial respiration was suspended), but on restarting the respiration the activity increased greatly. After injecting lobeline, the activity increased during inflation or deflation or in both phases of the respiratory cycle. It also increased greatly during deflation produced by suction of air from the lungs after lobeline. Such presumed increased activity in the RARs of man produced by forced expiration to residual volume at the time lobeline-induced sensations were expected did not enhance the sensations in any subject. 4. In all the subjects tested, forced expiration alone, which should stimulate RARs, never produced a dry cough or sensations similar to those produced by lobeline.5. The results suggest that since the reflex respiratory effects of lobeline are due to J receptors, the sensations and cough can also be attributed to them, since both events occur at about the same time, and also because the RARs, and the slowly adapting receptors (SARs), do not seem to play a primary role in producing or potentiating the sensations

Extrinsic primary afferent signalling in the gut

Visceral sensory neurons activate reflex pathways that control gut function and also give rise to important sensations, such as fullness, bloating, nausea, discomfort, urgency and pain. Sensory neurons are organised into three distinct anatomical pathways to the central nervous system (vagal, thoracolumbar and lumbosacral). Although remarkable progress has been made in characterizing the roles of many ion channels, receptors and second messengers in visceral sensory neurons, the basic aim of understanding how many classes there are, and how they differ, has proven difficult to achieve. We suggest that just five structurally distinct types of sensory endings are present in the gut wall that account for essentially all of the primary afferent neurons in the three pathways. Each of these five major structural types of endings seems to show distinctive combinations of physiological responses. These types are: 'intraganglionic laminar' endings in myenteric ganglia; 'mucosal' endings located in the subepithelial layer; 'muscular–mucosal' afferents, with mechanosensitive endings close to the muscularis mucosae; 'intramuscular' endings, with endings within the smooth muscle layers; and 'vascular' afferents, with sensitive endings primarily on blood vessels. 'Silent' afferents might be a subset of inexcitable 'vascular' afferents, which can be switched on by inflammatory mediators. Extrinsic sensory neurons comprise an attractive focus for targeted therapeutic intervention in a range of gastrointestinal disorders.Australian National Health and Medical Research Counci

Changes in respiratory sensations induced by lobeline after human bilateral lung transplantation

The sensations evoked by the injection of lobeline into the right antecubital vein were studied in 8 subjects after bilateral lung transplantation and 10 control subjects. In control subjects, two distinct sensations were experienced. There was an early noxious sensation (onset ∼10 s) followed by a late sensation of breathlessness (onset ∼26 s) associated with involuntary hyperventilation. The early sensation was accompanied by respiratory and cardiovascular changes.In contrast to control subjects, the early respiratory events and the noxious sensations evoked by injections of lobeline (18–60 μg kg−1) did not occur in subjects with recent bilateral lung transplantation. This suggests that the early respiratory sensations are mediated by the discharge of receptors in the lungs.The late hyperventilation and the accompanying sensation of breathlessness occurred in both transplant and control subjects and are therefore likely to be mediated by receptors elsewhere in the body, presumably systemic arterial chemoreceptors stimulated by lobeline.In control subjects, but not transplant subjects, there was a consistent decrease in mean arterial pressure associated with the lobeline injection. This suggests that pulmonary afferents mediate the hypotension.For transplant subjects studied more than a year after transplantation, there was some evidence that the noxious respiratory sensations evoked by lobeline had returned. This suggests that some functional reinnervation of pulmonary afferents may occur