Bengt Pernow

Experimental immunohistochemical studies on the localization and distribution of substance P in cat primary sensory neurons.

With the indirect immunofluorescence technique of Coons and collaborators the occurrence of substance P (SP)-like immunoreactivity was studied in spinal ganglia (L6-S1), the spinal cord (L6-S1) and the pad skin of the hind paw of the cat. In untreated cats a very dense network of SP-positive fibers was found in the spinal cord in Lissauers fasciculus, in laminae I-III and a rather dense plexus was seen in the ventral horns, in the area around the central canal (laminae X) and in the medial parts of laminae VI and VII. SP-positive fibers were also observed in the connective tissue under the epithelium of the skin. However, in untreated cats no specific immunogluorescnece was observed in the spinal ganglia, dorsal roots or certain large peripheral nerve trunks. After certain experimental procedures such as local application of colchicine or compression of the dorsal root close to the spinal ganglion, SP-positive fluorescence was observed in a rather small number of neuronal cell bodies and in fibers. The fluorescent material was observed in the peripheral parts of the cytoplasm and the cell bodies were exclusively of the small type. Ten days after transection of the dorsal roots a marked decrease in the number of SP-positive fibers was observed in the substantia gelatinosa but not in the ventral horns. The present results give strong evidence for the occurrence of SP in a certain population of primary sensory neurons and support earlier findings that SP may act as a transmitter or modulator in these neurons.

Substance P: a pioneer amongst neuropeptides

Abstract.   Hökfelt T, Pernow B, Wahren J (Karolinska Institutet, Stockholm, Sweden). Substance P: a pioneer amongst neuropeptides. J Intern Med 2001; 249: 27–40.

Chapter 4 Coexistence of neuronal messengers — an overview

Publisher Summary This chapter discusses results demonstrating that neurons often contain more than one chemical compound. The different types of coexistence situations are described, including (1) a classical transmitter and one or more peptides, (2) more than one classical transmitter, and (3) a classical transmitter, a peptide, and adenosine triphosphate (ATP). The functional significance of these histochemical findings is at present difficult to evaluate, but in studies on the peripheral nervous system evidence has been obtained that classical transmitter and peptide are coreleased and interact in a cooperative way on effector cells. In addition to enhancement, there is evidence that other types of interactions may occur—for example, the peptide may inhibit the release of the classical transmitter. Also in the central nervous system (CNS), indirect evidence is present for similar mechanisms—that is, to strengthen transmission at synaptic (or non-synaptic) sites and for the peptide inhibition of release of a classical transmitter. Multiple messengers may provide the means for increasing the capacity for information transfer in the nervous system.

THE EFFECT OF LOCAL ANAESTHETICS ON THE CENTRAL CIRCULATION AND RESPIRATION IN MAN AND DOG1),2)

The effect on the central circulation and respiration of intravenously infused equipotent doses of mepivacaine and bupivacaine was studied in 11 healthy men and in four conscious dogs. The subconvulsive dose in man and dogs was 5 mg/kg b.w., for mepivacaine infused at a constant rate for 20 minutes, and 1.25 mg/kg b.w. for bupivacaine during the same infusion period. This infusion rate was increased fivefold in the dogs to produce seizures. Lidocaine 5 mg/kg b.w. was also infused in four volunteers for 20 minutes.

Localization of substance P-like immunoreactivity in nerves in the tooth pulp

&NA; The occurrence of substance P (SP)‐like immunoreactivity was studied in dental pulps of the cat. In untreated animals SP‐positive fibres were found in all areas of the pulp. Most fibres were seen in central parts of the pulp but they were also observed in relation to the odontoblasts. Single, possibly unmyelinated, or fine caliber fibres or small bundles of them were seen running close to large non‐fluorescent myelinated nerves, to blood vessels or without any obvious association with either of these structures. Fourteen days after transection of the inferior alveolar nerve no SP‐positive fibres were observed in pulps on the denervated side. Transection of the cervical sympathetic ganglion did not change the occurrence of SP‐positive fibres. The results indicate the existence of at least two types of afferent fibres in the dental pulp of the cat. Since the tooth pulp has been demonstrated to give rise only to pain sensation when stimulated, the results give morphological support for a role of SP neurones in pain transmission.

Uptake of individual free fatty acids by skeletal muscle and liver in man

Arterial-venous concentration differences for individual free fatty acids (FFA) were measured across the deep tissues of the forearm, the splanchnic vascular bed, and the kidney in healthy, postabsorptive subjects. In addition, arterial-portal venous FFA differences were determined in five patients undergoing elective cholecystectomy. The differences in fractional uptake among the individual FFA across the forearm were small and not statistically significant. Splanchnic fractional uptake was high for FFA with short chain lengths and rose with increasing degree of unsaturation. Small, negative arterial-portal venous differences for individual FFA were observed, indicating that arterial-hepatic venous FFA differences mainly reflect hepatic uptake. When the arterial FFA concentration was reduced to approximately 25% of the control values by the administration of nicotinic acid, net uptake of total FFA ceased but there was release of stearic acid and uptake of lauric, myristic, and palmitoleic acid to the splanchnic region. Muscle and liver uptakes of individual FFA were both dependent on their arterial concentrations with the exception of the splanchnic uptake of stearic acid. There was no uptake of free arachidonic acid by either muscle or liver, nor was there significant uptake of any of the free fatty acids by the kidney. It is concluded (a) that there are important quantitative differences between the net exchanges of individual FFA across the splanchnic vascular bed, (b) that tracer studies of FFA metabolism require the determination of individual FFA specific activities, (c) that palmitic and oleic acid appear to be suitable tracers for the entire FFA fraction in most instances.

Influence of Age on the Local Circulatory Adaptation to Leg Exercise

Blood flow and oxygen uptake of the leg and release of lactate were studied in a group of 7 healthy well-trained 52–59-year-old men at rest and during bicycle exercise at work loads that were increased in steps to near maximal levels of work intensity. The results were compared with those for 7 healthy subjects 25–30 years of age studied previously (11). Blood flow to the leg rose in linear proportion to pulmonary oxygen uptake at submaximal work intensities but tended to level off at the heaviest work loads. The rise in leg blood flow during exercise was less in the middle-aged group and was largely compensated for by a larger arterial-femoral venous oxygen difference during exercise. Leg release of lactate rose approximately exponentially in relation to work load. No difference was observed between the two age groups with regard to arterial lactate or net release of lactate during exercise. It is concluded that blood flow to the leg in middle-aged men rises in a curvilinear manner in response to exercis...

Experience with pindolol, a betareceptor blocker, in the treatment of hypertension.

Ten patients, mean age 48 years, with essential hypertension of stage I and II according to the WHO classification, were studied at rest and during work before and after an average of two and 16 months of oral treatment with the beta-adrenergic blocking agent, pindolol. The pindolol treatment caused a significant decrease in the systemic systolic and diastolic blood pressure, both at rest and during work. Three mechanisms seem to be involved in the antihypertensive effect of pindolol: (1) a negative chronotropic effect on the heart, (2) a decrease in peripheral vascular resistance, and (3) an increase in venous capacitance affecting the venous return. However, the significance of these mechanisms seems to differ when the situations after two months of treatment are compared with those after 16 months of treatment. In the beginning, a decrease in cardiac output seems to be the main cause of the lowering of the blood pressure; later, a decrease in systemic vascular resistance might be of greater importance.

PHARMACOLOGY OF SUBSTANCE P

The dominating pharmacological effects exerted by substance P can be referred to three organic systems, namely, the circulatory organs, the smooth muscle, particularly that of the gastro-intestinal tract, and the central nervous system. Its effect on the first two was already demonstrated in the initial publication on substance P by Euler and Gaddum in 1931, whereas the last-mentioned has attracted the greatest interest in recent years. The effects of substance P on the central and peripheral nervous system is discussed in this volume by Dr. Stern. Therefore, only the hemodynamic

THE EFFECT OF MEPIVACAINE AND LIDOCAINE ON FOREARM RESISTANCE AND CAPACITANCE VESSELS IN MAN

1 Mepivacaine and lidocaine were infused intravenously and into the brachial artery in healthy human subjects. The effects on arterial blood pressure, forearm blood flow, forearm vascular resistance and venous tone were studied. 2 Intravenous infusion of mepivacaine at a rate of 0.25 mg per kg body weight per min during 20 minutes increased the mean arterial blood pressure, forearm blood flow and venous tone. Blockade of the sympathetic nerves to the arm abolished die effect on blood flow, while the increase in blood pressure and venous tone persisted. 3 Intra‐arterial infusions of 0.5‐6 mg per min of mepivacaine increased the venous tone and decreased the forearm blood flow. The mean arterial blood pressure was unchanged, while the calculated forearm vascular resistance increased. Following sympadietic blockade, the effect on forearm vascular resistance and blood flow was almost completely eliminated, while the increase in venous tone persisted. 4 Intra‐arterial infusion of 1‐3 mg per min of lidocaine increased the venous tone, but did not significantly influence die arterial blood pressure of forearm blood flow.